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Study to Determine Efficacy and Safety of Lenalidomide Plus Low-dose Dexamethasone Versus Melphalan, Prednisone, Thalidomide in Patients With Previously Untreated Multiple Myeloma (FIRST)

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ClinicalTrials.gov Identifier: NCT00689936
Recruitment Status : Completed
First Posted : June 4, 2008
Results First Posted : August 11, 2017
Last Update Posted : November 20, 2019
Sponsor:
Information provided by (Responsible Party):
Celgene

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Myeloma
Interventions Drug: Lenalidomide and low-dose dexamethasone
Drug: Lenalidomide plus low-dose dexamethasone given for 18 four-week cycles
Drug: Melphalan, Prednisone and Thalidomide
Enrollment 1623
Recruitment Details This study was conducted in the Europe, Asia, North America and Pacific regions. Participants were randomized at 246 sites (165 in Europe, 23 in Asia, 39 in North America, and 19 in the Pacific). The study was co-sponsored by Intergroupe Francophone du Myélome (IFM) (for sites in France, Switzerland, and Belgium) and Celgene Corporation.
Pre-assignment Details Participants were stratified at randomization by 1) age (≤ 75 versus > 75 years), 2) stage (International Staging System Stages I or II versus Stage III), and 3) country.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Period Title: Active Treatment Phase
Started 535 541 547
Safety Population 532 [1] 540 [1] 541 [1]
Untreated 3 [2] 1 [2] 6 [2]
Completed 0 0 0
Not Completed 535 541 547
Reason Not Completed
Adverse Event             68             71             76
Disease Progression             273             362             339
Withdrawal by Subject             16             16             21
Death             60             28             37
Lost to Follow-up             0             2             2
Protocol Violation             2             2             4
Study Close Out             64             26             21
Miscellaneous             52             34             47
[1]
Safety population = all randomized participants who received at least 1 dose of study treatment.
[2]
Participants randomized, but did not receive any study drug treatment.
Period Title: Progression Free Survival-PFS-Follow-Up
Started 87 [1] 300 [2] 273 [3]
Completed 87 300 273
Not Completed 0 0 0
[1]
Includes participants who discontinued treatment for reasons other than progressive disease.
[2]
Includes participants who completed 18 cycles (Rd18) and did not experience progressive disease.
[3]
Includes participants who completed 12 cycles MPT and did not experience progressive disease.
Period Title: Long-Term Follow Up Phase
Started 382 [1] 463 [1] 459 [1]
Completed 255 275 315
Not Completed 127 188 144
Reason Not Completed
Continue in Long Term Follow Up             127             188             144
[1]
Includes participants from both the active treatment phase and from the PFS follow-up phase.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT) Total
Hide Arm/Group Description Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Total of all reporting groups
Overall Number of Baseline Participants 535 541 547 1623
Hide Baseline Analysis Population Description
Intent to Treat (ITT) population includes all participants who were randomized, independent of whether they received study treatment or not
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 535 participants 541 participants 547 participants 1623 participants
73.2  (6.57) 72.9  (6.50) 73.1  (6.32) 73.1  (6.46)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 535 participants 541 participants 547 participants 1623 participants
Female
241
  45.0%
268
  49.5%
260
  47.5%
769
  47.4%
Male
294
  55.0%
273
  50.5%
287
  52.5%
854
  52.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 535 participants 541 participants 547 participants 1623 participants
Asian 40 43 44 127
Black or African American 9 6 5 20
Native Hawaiian or other Pacific Islanders 1 0 1 2
White or Caucasian 474 480 491 1445
Other, Miscellaneous 6 11 3 20
Undisclosed 5 1 3 9
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 535 participants 541 participants 547 participants 1623 participants
Hispanic or Latino 37 33 36 106
Not Hispanic or Latino 493 505 508 1506
Undisclosed 5 3 3 11
International Staging System (ISS)   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 535 participants 541 participants 547 participants 1623 participants
Stage I 106 106 103 315
Stage II 227 229 225 681
Stage III 202 206 219 627
[1]
Measure Description: International Staging System (ISS) is used as a staging system for multiple myeloma and divides myeloma into 3 stages based only on the serum beta-2 microglobulin and serum albumin levels. Higher stages represent more advanced disease.
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 535 participants 541 participants 547 participants 1623 participants
0 (fully active) 155 163 156 474
1 (restrictive but ambulatory) 257 263 275 795
2 (ambulatory but unable to work) 119 113 111 343
3-4 (limited self-care, completely disabled) 2 2 2 6
Missing 2 0 3 5
[1]
Measure Description: Eastern Cooperative Oncology Group (ECOG) Performance Status is used to assess the progress of disease in a patient, how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis.
Creatinine clearance  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 535 participants 541 participants 547 participants 1623 participants
>=60 ml/min 269 280 285 834
<60 ml/min 266 261 261 788
Missing 0 0 1 1
Beta2 Microglobulin  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 535 participants 541 participants 547 participants 1623 participants
>5.5 mg/L 224 224 234 682
<=5.5 mg/L 309 316 312 937
Missing 2 1 1 4
Albumin  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 535 participants 541 participants 547 participants 1623 participants
<=35 g/L 192 209 223 624
> 35 g/L 343 331 324 998
Missing 0 1 0 1
Lactic Dehydrogenase  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 535 participants 541 participants 547 participants 1623 participants
<200 U/L 448 442 434 1324
>=200 U/L 86 99 112 297
Missing 1 0 1 2
Multiple Myeloma Subtype  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 535 participants 541 participants 547 participants 1623 participants
Immunoglobulin A 138 142 123 403
Immunoglobulin A and Immunoglobulin G 7 6 8 21
Immunoglobulin A and Immunoglobulin M 0 0 1 1
Immunoglobulin D 4 7 4 15
Immunoglobulin G 334 331 350 1015
Immunoglobulin M 3 1 1 5
Not available (includes light-chain disease) 49 54 60 163
Cytogenetic Risk   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 535 participants 541 participants 547 participants 1623 participants
Adverse Risk 170 185 189 544
Favorable Hyperdiploidy 112 103 102 317
Normal 148 131 141 420
Uncertain Risk 38 56 40 134
Not evaluable 34 35 44 113
Missing 33 31 31 95
[1]
Measure Description: Cytogenetic risk categories are mutually exclusive. Definitions: Adverse risk category: t(4:14), t(14:16), del (13q) or monosomy 13, del (17p), 1q gain; Non-adverse risk categories include favorable hyperdiploidy: t(11:14), gains of 5/9/15; normal: a normal result, gains other than 5/9/15, IgH deletion, and uncertain risk: probes used for analysis cannot place participant in any risk categories. Not evaluable: no specimen received, test failure or insufficient number of cells available for analysis.
1.Primary Outcome
Title Kaplan-Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Independent Review Adjudication Committee (IRAC)
Hide Description PFS was calculated as the time from randomization to the first documented PD or death due to any cause during the study, which ever occurred first based on the International Myeloma Working Group Uniform Response criteria (IMWG). Those who withdrew for any reason or received another anti-myeloma therapy without documented PD were censored on the date of their last response assessment, prior to receiving any other anti-myeloma therapy. Censoring rules for PFS: - No baseline assessments and no progression or death documented within the 2 scheduled assessments; Death within the lst two assessments without any adequate response assessment; Progression documented between scheduled assessments; Death between adequate assessments; no progression; study discontinuations for reasons other than PD or death; new anti-myeloma started prior to PD; death or PD after an extended lost to follow-up time period (2 or more missed scheduled assessment's).
Time Frame From date of randomization until the data cut-off date of 24 May 2013. Median follow-up time for all participants was 17.1 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat (ITT) population included all participants who were randomized, independent of whether they received study treatment or not.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 535 541 547
Median (95% Confidence Interval)
Unit of Measure: months
25.5
(20.7 to 29.4)
20.7
(19.4 to 22.0)
21.2
(19.3 to 23.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00006
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.61 to 0.85
Estimation Comments Based on stratified Cox proportional hazards model comparing the hazard functions associated with treatment groups.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Lenalidomide and Dexamethasone Rd18
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00001
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.60 to 0.82
Estimation Comments Based on stratified Cox proportional hazards model comparing the hazard functions associated with treatment groups.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Dexamethasone Rd18, Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.70349
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.89 to 1.20
Estimation Comments Based on stratified Cox proportional hazards model comparing the hazard functions associated with treatment groups.
2.Primary Outcome
Title Kaplan-Meier Estimates of PFS Based on the Response Assessment by the Investigator At the Time of Final Analysis
Hide Description PFS was calculated as the time from randomization to the first documented PD or death due to any cause during the study, which ever occurred first based on the International Myeloma Working Group Uniform Response criteria (IMWG). Those who withdrew for any reason or received another anti-myeloma therapy without documented PD were censored on the date of their last response assessment, prior to receiving any other anti-myeloma therapy. Censoring rules for PFS: - No baseline assessments and no progression or death documented within the 2 scheduled assessments; Death within the lst two assessments without any adequate response assessment; Progression documented between scheduled assessments; Death between adequate assessments; no progression; study discontinuations for reasons other than PD or death; new anti-myeloma started prior to PD; death or PD after an extended lost to follow-up time period (2 or more missed scheduled assessment's).
Time Frame From date of randomization to date of data cut-off date of 21 January 2016; median follow-up for all participants was 17.7 months
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat population included all participants who were randomized, independent of whether they received study treatment or not.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 535 541 547
Median (95% Confidence Interval)
Unit of Measure: months
26.0
(20.7 to 29.7)
21.0
(19.7 to 22.4)
21.9
(19.8 to 23.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.59 to 0.79
Estimation Comments Based on a stratified Cox proportional hazards model
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Lenalidomide and Dexamethasone Rd18
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.60 to 0.81
Estimation Comments Based on a stratified Cox proportional hazards model
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Dexamethasone Rd18, Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.91161
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.86 to 1.14
Estimation Comments Based on a stratified Cox proportional hazards model
3.Secondary Outcome
Title Kaplan Meier Estimates of Overall Survival at the Time of Final Analysis (OS)
Hide Description Overall survival was defined as the time between randomization and death. Participants, who died, regardless of the cause of death, were considered to have had an event. All participants who were lost to follow-up prior to the end of the trial or who were withdrawn from the trial were censored at the time of last contact. Participants who were still being treated were censored at the last available date the participant was known to be alive.
Time Frame From date of randomization to date of data cut-off date of 21 January 2016; median follow-up for all participants was 48.3 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized, independent of whether they received study treatment or not.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 535 541 547
Median (95% Confidence Interval)
Unit of Measure: months
59.1
(53.9 to 65.9)
62.3
(53.6 to 68.7)
49.1
(44.3 to 53.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00234
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.67 to 0.92
Estimation Comments Based on a stratified Cox proportional hazards model
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Lenalidomide and Dexamethasone Rd18
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.82903
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.86 to 1.20
Estimation Comments Based on a stratified Cox proportional hazards model
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Dexamethasone Rd18, Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00119
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.66 to 0.90
Estimation Comments Based on a stratified Cox proportional hazards model
4.Secondary Outcome
Title Percentage of Participants With an Objective Response Based on IRAC Review
Hide Description Objective response according to IMWG Uniform Response Criteria was defined as a best overall response including a complete response (CR), very good partial response (VGPR) or partial response (PR) based on the IRAC Review. A CR is defined as: negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in BM; A VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to <200 mg/24 hours. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.
Time Frame Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population includes all participants who were randomized, independent of whether they received study treatment or not.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 535 541 547
Measure Type: Number
Unit of Measure: percentage of participants
75.1 73.4 62.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.83
Confidence Interval (2-Sided) 95%
1.41 to 2.37
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Lenalidomide and Dexamethasone Rd18
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.53065
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.83 to 1.44
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Dexamethasone Rd18, Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00010
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.67
Confidence Interval (2-Sided) 95%
1.29 to 2.15
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With an Objective Response Based on Investigator Assessment at Time of Final Analysis
Hide Description Objective response according to IMWG Uniform Response Criteria was defined as a best overall response including a complete response (CR), very good partial response (VGPR) or partial response (PR) based on the IRAC Review. A CR is defined s: negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in BM; A VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to <200 mg/24 hours. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.
Time Frame Disease response was assessed every 28 days until end of treatment or the data cut-off date of 21 January 2016; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population includes all participants who were randomized, independent of whether they received study treatment or not.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 535 541 547
Measure Type: Number
Unit of Measure: percentage of participants
80.7 78.6 67.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.02
Confidence Interval (2-Sided) 95%
1.53 to 2.68
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Lenalidomide and Dexamethasone Rd18
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.40500
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
0.85 to 1.54
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Dexamethasone Rd18, Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00004
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.77
Confidence Interval (2-Sided) 95%
1.35 to 2.32
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Kaplan Meier Estimates of Duration of Myeloma Response as Determined by the IRAC
Hide Description Duration of response was defined as the duration from the time when the response criteria were first met for CR or VGPR or PR based on IMWG criteria until the first date the response criteria were met for progressive disease or until the participant died from any cause, whichever occurred first.
Time Frame Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median follow-up for responders was 20.1 months
Hide Outcome Measure Data
Hide Analysis Population Description
Study participants with at least a PR
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 402 397 341
Median (95% Confidence Interval)
Unit of Measure: months
35.0
(27.9 to 43.4)
22.1
(20.3 to 24.0)
22.3
(20.2 to 24.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.51 to 0.76
Estimation Comments Based on unstratified Cox proportional hazards model.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Lenalidomide and Dexamethasone Rd18
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
0.50 to 0.72
Estimation Comments Based on unstratified Cox proportional hazards model.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Dexamethasone Rd18, Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.76740
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.86 to 1.23
Estimation Comments Based on unstratified Cox proportional hazards model.
7.Secondary Outcome
Title Kaplan Meier Estimates of Duration of Myeloma Response as Determined by an Investigator Assessment at Time of Final Analysis
Hide Description Duration of response was defined as the duration from the time when the response criteria were first met for CR or VGPR or PR based on IMWG criteria until the first date the response criteria were met for progressive disease or until the participant died from any cause, whichever occurred first.
Time Frame Disease response was assessed every 28 days until end of treatment; data cut-off date of 21 January 2016; median follow-up for responders was 19.9 months
Hide Outcome Measure Data
Hide Analysis Population Description
Study participants with at least a PR
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 432 425 369
Median (95% Confidence Interval)
Unit of Measure: months
31.5
(26.2 to 37.3)
21.5
(19.2 to 23.0)
22.1
(20.3 to 24.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.51 to 0.72
Estimation Comments Based on a stratified Cox proportional hazards model
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Lenalidomide and Dexamethasone Rd18
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.52 to 0.72
Estimation Comments Based on a stratified Cox proportional hazards model
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Dexamethasone Rd18, Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.99537
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.85 to 1.17
Estimation Comments Based on a stratified Cox proportional hazards model
8.Secondary Outcome
Title Time to First Response Based on the Review by the IRAC
Hide Description The time to first myeloma response was defined as the time from randomization to the time when the response criteria for at least a PR was first met based on the IMWG criteria.
Time Frame Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had at least a PR.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 402 397 341
Median (Full Range)
Unit of Measure: months
1.8
(0.7 to 22.2)
1.8
(0.8 to 17.1)
2.8
(1.3 to 49.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Lenalidomide and Dexamethasone Rd18
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.46672
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Dexamethasone Rd18, Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
9.Secondary Outcome
Title Time to First Response Based on the Investigator Assessment at the Time of Final Analysis
Hide Description The time to first myeloma response was defined as the time from randomization to the time when the response criteria for at least a PR was first met based on the IMWG criteria assessed by the investigator.
Time Frame Disease response was assessed every 28 days until end of treatment or the data cut-off date of 21 January 2016; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had at least a PR.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 430 425 368
Median (Full Range)
Unit of Measure: months
1.8
(0.5 to 22.2)
1.8
(0.8 to 34.8)
2.8
(1.2 to 56.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Lenalidomide and Dexamethasone Rd18
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.46987
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Dexamethasone Rd18, Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
10.Secondary Outcome
Title Kaplan Meier Estimates of Time to Treatment Failure (TTF)
Hide Description TTF is defined as the time between the randomization and discontinuation of study treatment for any reason, including disease progression (determined by IRAC based on the IMWG response criteria), treatment toxicity, start of another anti-myeloma therapy (AMT) or death.
Time Frame From date of randomization until the data cut-off of 24 May 2013; median follow-up for all participants was 16.1 months.
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population includes participants who were randomized, independent of whether they received study treatment or not
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 535 541 547
Median (95% Confidence Interval)
Unit of Measure: months
16.9
(14.1 to 18.4)
17.2
(14.6 to 18.2)
14.1
(12.0 to 16.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00012
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.68 to 0.88
Estimation Comments Based on a stratified Cox proportional hazards model
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Lenalidomide and Dexamethasone Rd18
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00187
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.71 to 0.93
Estimation Comments Based on a stratified Cox proportional hazards model
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Dexamethasone Rd18, Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.45973
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.84 to 1.08
Estimation Comments Based on a stratified Cox proportional hazards model
11.Secondary Outcome
Title Kaplan Meier Estimates of Time to Treatment Failure (TTF) at the Time of Final Analysis
Hide Description TTF is defined as the time between the randomization and discontinuation of study treatment for any reason, including disease progression (determined by the investigators assessment based on the IMWG response criteria), treatment toxicity, start of another anti-myeloma therapy (AMT) or death.
Time Frame From date of randomization until the data cut-off date of 21 January 2016; median follow up for all participants was 16.1 months.
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population includes participants who were randomized, independent of whether they received study treatment or not
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 535 541 547
Median (95% Confidence Interval)
Unit of Measure: months
16.9
(14.1 to 18.4)
17.2
(14.6 to 18.2)
14.1
(12.0 to 16.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00002
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
0.67 to 0.86
Estimation Comments Based on a stratified Cox proportional hazards model
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Lenalidomide and Dexamethasone Rd18
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00126
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.72 to 0.92
Estimation Comments Based on a stratified Cox proportional hazards model
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Dexamethasone Rd18, Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.27704
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.83 to 1.06
Estimation Comments Based on a stratified Cox proportional hazards model
12.Secondary Outcome
Title Kaplan Meier Estimates for Time to Second-line Anti-myeloma Treatment (AMT)
Hide Description Time to second-line anti-myeloma therapy was defined as time from randomization to the start of another non-protocol anti-myeloma therapy.
Time Frame From date of randomization until the data cut-off of 24 May 2013; median follow-up for all participants was 23.0 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population includes all participants who were randomized, independent of whether they received study treatment or not
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 535 541 547
Median (95% Confidence Interval)
Unit of Measure: months
39.1 [1] 
(32.8 to NA)
28.5
(26.9 to 30.4)
26.7
(24.0 to 29.9)
[1]
Could not be estimated due to the low number of events at the time of analysis
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.56 to 0.78
Estimation Comments Based on a stratified Cox proportional hazards model
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Lenalidomide and Dexamethasone Rd18
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00067
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.63 to 0.88
Estimation Comments Based on a stratified Cox proportional hazards model
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Dexamethasone Rd18, Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12333
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.75 to 1.03
Estimation Comments Based on a stratified Cox proportional hazards model
13.Secondary Outcome
Title Kaplan Meier Estimates of Time to Second Line Therapy AMT at the Time of Final Analysis
Hide Description Time to second-line anti-myeloma therapy is defined as time from randomization to the start of another non-protocol anti-myeloma therapy. Those who do not receive another anti-myeloma therapy were censored at the last assessment or follow-up visit known to have received no new therapy.
Time Frame From date of randomization until the data cut-off of date 21 January 2016; median follow-up for all participants was 23.0 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population includes all participants who were randomized, independent of whether they received study treatment or not.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 535 541 547
Median (Full Range)
Unit of Measure: months
36.7
(31.9 to 45.2)
28.5
(26.9 to 30.4)
26.7
(24.0 to 29.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.00001
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.54 to .73
Estimation Comments Based on unstratified Cox proportional hazards model.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Lenalidomide and Dexamethasone Rd18
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00001
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.61 to 0.83
Estimation Comments Based on unstratified Cox proportional hazards model.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Dexamethasone Rd18, Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.05821
Comments The p-value is based on the unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.76 to 1.00
Estimation Comments Based on unstratified Cox proportional hazards model.
14.Secondary Outcome
Title Percentage of Participants With an Objective Response After Second-line Anti-myeloma Treatment at the Time of Final Analysis
Hide Description Objective response according to IMWG Uniform Response Criteria was defined as a best overall response including a complete response (CR), very good partial response (VGPR) or partial response (PR) based on the IRAC Review. A CR is defined s: negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in BM; A VGPR is serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to <200 mg/24 hours. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.
Time Frame Disease response was assessed every 28 days until end of treatment; data cut-off date of 21 January 2016; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; Participants with second line AMT.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 299 377 381
Measure Type: Number
Unit of Measure: percentage of participants
46.2 53.1 45.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.93824
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.75 to 1.38
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Lenalidomide and Dexamethasone Rd18
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.08836
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
0.56 to 1.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Dexamethasone Rd18, Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04974
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.34
Confidence Interval (2-Sided) 95%
1.01 to 1.79
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Percentage of Participants With a Myeloma Response by Adverse Risk Cytogenetic Risk Category Based on IRAC Review.
Hide Description Participants were placed in adverse and non-adverse cytogenetic risk categories at baseline and response rates evaluated. Adverse Risk: t(4;14), t(14;16), del(13q) or monosomy 13, del(17p), 1q gain Favorable Hyperdiploidy: : t(11;14), gains of 5/9/15; Normal: a normal result, gains other than 5/9/15, IgH deletion Uncertain risk: probes used for analysis cannot place participant in any of the other risk categories. Objective response = best overall response including CR, VGPR or PR based on the IRAC Review; A CR is negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in BM; A VGPRis serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to <200 mg/24 hours. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.
Time Frame Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population with Cytogenetic risk of Adverse Risk
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 170 185 189
Measure Type: Number
Unit of Measure: Percentage of participants
70.0 69.7 58.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02134
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.68
Confidence Interval (2-Sided) 95%
1.08 to 2.59
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Lenalidomide and Dexamethasone Rd18
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.00000
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.64 to 1.59
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Dexamethasone Rd18, Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02374
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.65
Confidence Interval (2-Sided) 95%
1.08 to 2.53
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Percentage of Participants With a Myeloma Response by Favorable Hyperdiploidy Risk Cytogenetic Risk Category Based on IRAC Review
Hide Description Participants were placed in adverse and non-adverse cytogenetic risk categories at baseline and response rates evaluated. Adverse Risk: t(4;14), t(14;16), del(13q) or monosomy 13, del(17p), 1q gain Favorable Hyperdiploidy: : t(11;14), gains of 5/9/15; Normal: a normal result, gains other than 5/9/15, IgH deletion Uncertain risk: probes used for analysis cannot place participant in any of the other risk categories. Objective response = best overall response including CR, VGPR or PR based on the IRAC Review; A CR is negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in BM; A VGPRis serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to <200 mg/24 hours. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.
Time Frame Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population with a Cytogenetic Risk of Favorable Hyperploidy
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 112 103 102
Measure Type: Number
Unit of Measure: percentage of participants
80.4 81.6 70.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.11152
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.70
Confidence Interval (2-Sided) 95%
0.91 to 3.21
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Lenalidomide and Dexamethasone Rd18
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.86336
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.47 to 1.83
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Dexamethasone Rd18, Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07321
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.84
Confidence Interval (2-Sided) 95%
0.96 to 3.55
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Percentage of Participants With a Myeloma Response by Normal Risk Cytogenetic Risk Category Based on IRAC Review
Hide Description Participants were placed in adverse and non-adverse cytogenetic risk categories at baseline and response rates evaluated. Adverse Risk: t(4;14), t(14;16), del(13q) or monosomy 13, del(17p), 1q gain Favorable Hyperdiploidy: : t(11;14), gains of 5/9/15; Normal: a normal result, gains other than 5/9/15, IgH deletion Uncertain risk: probes used for analysis cannot place participant in any of the other risk categories. Objective response = best overall response including CR, VGPR or PR based on the IRAC Review; A CR is negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in BM; A VGPRis serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to <200 mg/24 hours. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.
Time Frame Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population with a cytogenetic risk of normal
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 148 131 141
Measure Type: Number
Unit of Measure: percentage of particpants
80.4 74.8 61.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.00043
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.62
Confidence Interval (2-Sided) 95%
1.55 to 4.45
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Lenalidomide and Dexamethasone Rd18
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.31274
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.38
Confidence Interval (2-Sided) 95%
0.78 to 2.43
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Dexamethasone Rd18, Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01936
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.90
Confidence Interval (2-Sided) 95%
1.13 to 3.19
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Percentage of Participants With a Myeloma Response by Uncertain Risk Cytogenetic Risk Category Based on IRAC Review
Hide Description Participants were placed in adverse and non-adverse cytogenetic risk categories at baseline and response rates evaluated. Adverse Risk: t(4;14), t(14;16), del(13q) or monosomy 13, del(17p), 1q gain Favorable Hyperdiploidy: : t(11;14), gains of 5/9/15; Normal: a normal result, gains other than 5/9/15, IgH deletion Uncertain risk: probes used for analysis cannot place participant in any of the other risk categories. Objective response = best overall response including CR, VGPR or PR based on the IRAC Review; A CR is negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in BM; A VGPRis serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; A PR is ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to <200 mg/24 hours. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.
Time Frame Disease response was assessed every 28 days until end of treatment or the data cut-off date of 24 May 2013; median duration of treatment was 80.2 weeks in the Rd arm; 72 weeks in the Rd18 arm and 67.1 weeks in the MPT arm
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population with a Cytogenetic Risk of Uncertain Risk
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 38 56 40
Measure Type: Number
Unit of Measure: percentage of participants
60.5 76.8 57.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.82128
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.13
Confidence Interval (2-Sided) 95%
0.46 to 2.80
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Low-Dose Dexamethasone (Rd), Lenalidomide and Dexamethasone Rd18
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.11041
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.46
Confidence Interval (2-Sided) 95%
0.19 to 1.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Lenalidomide and Dexamethasone Rd18, Melphalan + Prednisone + Thalidomide (MPT)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.07302
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.44
Confidence Interval (2-Sided) 95%
1.01 to 5.91
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in QOL or functioning and positive values indicate improvement.
Time Frame Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
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Hide Analysis Population Description
Intent to Treat (ITT) population with available data.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 508 507 508
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 1 Number Analyzed 438 participants 441 participants 415 participants
0.4  (23.98) -1.3  (23.93) 1.0  (23.68)
Month 3 Number Analyzed 421 participants 413 participants 396 participants
4.8  (24.15) 4.7  (25.15) 4.3  (26.04)
Month 6 Number Analyzed 369 participants 376 participants 351 participants
5.9  (25.93) 5.4  (23.88) 6.1  (25.98)
Month 12 Number Analyzed 302 participants 299 participants 252 participants
4.8  (26.42) 3.2  (25.38) 6.5  (25.90)
Month 18 Number Analyzed 246 participants 238 participants 178 participants
6.4  (28.02) 5.7  (24.86) 4.8  (27.05)
Study discontinuation Number Analyzed 203 participants 261 participants 257 participants
-0.1  (27.07) 5.0  (27.33) 0.3  (28.07)
20.Secondary Outcome
Title Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Physical Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time Frame Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population with available data.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 511 514 509
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 1 Number Analyzed 445 participants 449 participants 419 participants
-1.7  (21.11) -1.4  (19.56) -0.9  (21.28)
Month 3 Number Analyzed 426 participants 421 participants 396 participants
3.4  (23.33) 4.7  (22.94) 2.2  (23.68)
Month 6 Number Analyzed 376 participants 382 participants 352 participants
4.7  (25.09) 7.6  (22.85) 5.3  (24.52)
Month 12 Number Analyzed 307 participants 302 participants 253 participants
5.0  (25.65) 7.4  (23.40) 6.9  (27.22)
Month 18 Number Analyzed 247 participants 243 participants 183 participants
6.9  (26.71) 6.8  (23.58) 8.3  (27.10)
Discontinuation Visit Number Analyzed 207 participants 267 participants 256 participants
-0.1  (29.70) 3.0  (27.32) -0.1  (27.58)
21.Secondary Outcome
Title Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Role Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time Frame Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population with available data.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 509 508 508
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 1 Number Analyzed 442 participants 445 participants 415 participants
-2.7  (29.94) -4.6  (28.20) -2.4  (30.48)
Month 3 Number Analyzed 422 participants 419 participants 395 participants
2.4  (33.32) 6.3  (32.43) 4.1  (34.23)
Month 6 Number Analyzed 373 participants 378 participants 352 participants
6.3  (35.44) 8.6  (32.42) 8.2  (36.09)
Month 12 Number Analyzed 305 participants 300 participants 252 participants
7.8  (36.60) 9.4  (34.15) 11.8  (38.94)
Month 18 Number Analyzed 245 participants 240 participants 182 participants
8.0  (35.34) 9.1  (34.35) 14.5  (39.03)
Discontinuation Visit Number Analyzed 206 participants 264 participants 256 participants
-0.3  (39.58) 3.8  (36.34) -1.0  (38.41)
22.Secondary Outcome
Title Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Emotional Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time Frame Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population with available data.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 509 510 510
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 1 Number Analyzed 443 participants 446 participants 419 participants
0.6  (22.13) 0.1  (20.73) 1.0  (21.52)
Month 3 Number Analyzed 423 participants 415 participants 397 participants
3.8  (22.29) 3.9  (22.11) 2.1  (22.27)
Month 6 Number Analyzed 375 participants 379 participants 351 participants
4.6  (24.36) 5.8  (22.39) 5.5  (22.55)
Month 12 Number Analyzed 305 participants 301 participants 254 participants
4.6  (24.08) 4.9  (22.23) 5.1  (22.37)
Month 18 Number Analyzed 246 participants 242 participants 179 participants
5.8  (25.61) 3.1  (23.31) 5.1  (22.99)
Discontinuation Visit Number Analyzed 205 participants 263 participants 256 participants
2.6  (24.30) 3.7  (23.77) -0.0  (24.72)
23.Secondary Outcome
Title Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Cognitive Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time Frame Cycle 1 Day 1, (Baseline) then Months 1, 3, 6, 12, 18 and Discontinuation visit
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population with available data.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 509 510 510
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 1 Number Analyzed 443 participants 447 participants 419 participants
-1.2  (21.73) -1.7  (19.08) -1.8  (24.07)
Month 3 Number Analyzed 424 participants 415 participants 397 participants
-0.7  (22.89) 1.8  (20.94) -1.5  (24.02)
Month 6 Number Analyzed 375 participants 379 participants 353 participants
-0.9  (22.57) 0.9  (19.77) -0.3  (23.55)
Month 12 Number Analyzed 306 participants 301 participants 254 participants
-1.6  (25.05) -1.2  (20.19) -0.6  (22.97)
Month 18 Number Analyzed 246 participants 242 participants 179 participants
-2.2  (25.61) -2.8  (20.97) -0.7  (23.99)
Discontinuation Visit Number Analyzed 206 participants 263 participants 256 participants
-4.9  (27.57) -2.6  (22.34) -7.1  (25.15)
24.Secondary Outcome
Title Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Social Functioning Scale is scored between 0 and 100, with a high score indicating better functioning/support. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time Frame Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population with available data.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 505 503 503
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 1 Number Analyzed 439 participants 441 participants 414 participants
-4.3  (29.10) -2.2  (27.44) -1.4  (30.52)
Month 3 Number Analyzed 419 participants 410 participants 389 participants
0.7  (29.36) 2.0  (30.93) 2.4  (30.70)
Month 6 Number Analyzed 374 participants 374 participants 348 participants
4.0  (32.48) 5.2  (28.50) 3.4  (35.24)
Month 12 Number Analyzed 305 participants 298 participants 252 participants
2.9  (34.96) 3.8  (32.29) 5.8  (33.68)
Month 18 Number Analyzed 247 participants 239 participants 177 participants
4.2  (34.99) 3.2  (31.67) 6.0  (35.20)
Discontinuation Visit Number Analyzed 204 participants 257 participants 254 participants
-1.2  (33.50) 2.7  (33.37) -3.5  (33.20)
25.Secondary Outcome
Title Change From Baseline in the EORTC QLQ-C30 Fatigue Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms.
Time Frame Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population with available data.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 511 514 512
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 1 Number Analyzed 445 participants 448 participants 421 participants
2.6  (25.32) 4.4  (24.03) 2.8  (25.44)
Month 3 Number Analyzed 425 participants 423 participants 400 participants
-2.5  (28.15) -3.4  (25.16) -1.8  (28.53)
Month 6 Number Analyzed 376 participants 383 participants 355 participants
-3.7  (28.54) -5.9  (26.37) -4.5  (29.09)
Month 12 Number Analyzed 306 participants 303 participants 255 participants
-4.3  (29.47) -2.3  (26.63) -3.9  (29.56)
Month 18 Number Analyzed 244 participants 242 participants 184 participants
-3.1  (29.82) 0.1  (29.12) -4.3  (30.05)
Discontinuation Visit Number Analyzed 207 participants 267 participants 258 participants
0.3  (29.75) -1.6  (29.11) 2.7  (30.15)
26.Secondary Outcome
Title Change From Baseline in the EORTC QLQ-C30 Pain Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Pain Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms.
Time Frame Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population with available data.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 511 514 512
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 1 Number Analyzed 446 participants 453 participants 423 participants
-5.4  (31.89) -4.4  (30.70) -7.8  (30.93)
Month 3 Number Analyzed 426 participants 423 participants 399 participants
-13.4  (34.28) -13.1  (32.32) -12.1  (31.98)
Month 6 Number Analyzed 379 participants 384 participants 355 participants
-14.4  (35.64) -16.1  (33.44) -13.4  (34.45)
Month 12 Number Analyzed 306 participants 304 participants 255 participants
-14.0  (36.05) -14.7  (32.34) -14.3  (32.85)
Month 18 Number Analyzed 248 participants 242 participants 183 participants
-14.4  (35.03) -12.4  (35.28) -14.7  (32.81)
Discontinuation Visit Number Analyzed 207 participants 266 participants 259 participants
-8.0  (39.37) -7.9  (37.65) -6.0  (37.09)
27.Secondary Outcome
Title Change From Baseline in the EORTC QLQ-C30 Nausea/Vomiting Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Nausea/Vomiting Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms.
Time Frame Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population with available data.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 511 513 512
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 1 Number Analyzed 446 participants 449 participants 424 participants
1.8  (20.05) -0.5  (23.19) 4.0  (22.91)
Month 3 Number Analyzed 426 participants 422 participants 399 participants
-1.1  (19.42) -2.5  (21.92) -1.2  (19.89)
Month 6 Number Analyzed 377 participants 381 participants 355 participants
-1.3  (18.53) -4.0  (21.52) -3.9  (19.57)
Month 12 Number Analyzed 306 participants 302 participants 255 participants
-2.2  (17.16) -3.6  (18.86) -3.9  (19.09)
Month 18 Number Analyzed 246 participants 242 participants 184 participants
-2.3  (19.20) -2.7  (18.92) -3.9  (19.44)
Discontinuation Visit Number Analyzed 206 participants 267 participants 258 participants
0.4  (21.43) -4.2  (24.37) 1.0  (21.46)
28.Secondary Outcome
Title Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnoea Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms.
Time Frame Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population includes all participants with available data.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 509 508 506
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 1 Number Analyzed 439 participants 440 participants 417 participants
0.9  (30.87) 3.6  (29.85) 4.2  (32.04)
Month 3 Number Analyzed 423 participants 417 participants 390 participants
-0.8  (31.87) -1.9  (29.45) 2.0  (32.49)
Month 6 Number Analyzed 372 participants 375 participants 351 participants
-2.3  (33.12) -2.9  (29.66) 0.1  (30.29)
Month 12 Number Analyzed 303 participants 294 participants 253 participants
-3.5  (30.97) -1.6  (29.23) -1.6  (32.76)
Month 18 Number Analyzed 244 participants 238 participants 182 participants
-1.8  (32.73) 2.9  (28.33) 0.4  (32.68)
Discontinuation Visit Number Analyzed 204 participants 262 participants 255 participants
-1.0  (37.42) 0.8  (31.01) 7.8  (33.72)
29.Secondary Outcome
Title Change From Baseline in the EORTC QLQ-C30 Insomnia Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Insomnia Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate improvement in symptoms and positive values indicate worsening symptoms.
Time Frame Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) population with available data.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 510 513 511
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 1 Number Analyzed 443 participants 447 participants 421 participants
2.1  (33.34) 3.2  (34.32) -10.5  (30.47)
Month 3 Number Analyzed 422 participants 420 participants 399 participants
0.2  (35.11) -1.3  (33.54) -8.9  (35.28)
Month 6 Number Analyzed 379 participants 382 participants 353 participants
-1.2  (34.84) -1.9  (31.43) -11.6  (32.96)
Month 12 Number Analyzed 303 participants 300 participants 253 participants
-1.0  (34.78) 1.1  (32.47) -9.6  (31.00)
Month 18 Number Analyzed 243 participants 241 participants 182 participants
-0.5  (37.11) 1.4  (35.72) -6.0  (34.42)
Discontinuation Visit Number Analyzed 204 participants 265 participants 254 participants
-5.2  (36.47) -1.6  (31.27) -4.5  (36.98)
30.Secondary Outcome
Title Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Appetite Loss Scale is scored between 0 and 100, with a high score indicating a higher level of appetite loss. Negative change from Baseline values indicate improvement in appetite and positive values indicate worsening of appetite.
Time Frame Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population with available data.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 509 512 510
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 1 Number Analyzed 442 participants 447 participants 422 participants
1.3  (33.46) 2.9  (31.87) 1.0  (32.35)
Month 3 Number Analyzed 424 participants 421 participants 396 participants
-5.9  (38.34) -3.3  (35.25) -6.2  (35.03)
Month 6 Number Analyzed 374 participants 381 participants 354 participants
-9.8  (40.02) -8.6  (33.98) -13.5  (35.98)
Month 12 Number Analyzed 307 participants 299 participants 253 participants
-7.3  (37.07) -6.4  (35.30) -10.5  (34.16)
Month 18 Number Analyzed 246 participants 241 participants 183 participants
-8.1  (35.97) -5.1  (33.29) -12.2  (31.88)
Discontinuation Visit Number Analyzed 203 participants 267 participants 257 participants
-1.0  (36.77) -7.5  (37.49) -2.6  (37.18)
31.Secondary Outcome
Title Change From Baseline in the EORTC QLQ-C30 Constipation Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Constipation Scale is scored between 0 and 100, with a high score indicating a higher level of constipation. Negative change from Baseline values indicate improvement in constipation and positive values indicate worsening of constipation.
Time Frame Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population with available data.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
Hide Arm/Group Description:
Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 508 511 510
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 1 Number Analyzed 441 participants 446 participants 419 participants
8.3  (36.74) 6.3  (36.18) 18.4  (41.23)
Month 3 Number Analyzed 422 participants 416 participants 397 participants
1.8  (37.53) 0.0  (37.02) 13.9  (39.30)
Month 6 Number Analyzed 373 participants 377 participants 353 participants
-2.4  (37.51) -5.1  (37.39) 6.8  (40.41)
Month 12 Number Analyzed 304 participants 301 participants 255 participants
-2.4  (38.79) -5.2  (38.09) 3.7  (38.28)
Month 18 Number Analyzed 246 participants 242 participants 179 participants
-4.5  (35.42) -5.9  (36.65) 0.0  (37.06)
Discontinuation Visit Number Analyzed 203 participants 261 participants 257 participants
-7.9  (39.98) -7.5  (39.20) -2.2  (38.86)
32.Secondary Outcome
Title Change From Baseline in the EORTC QLQ-C30 Diarrhea Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Diarrhea Scale is scored between 0 and 100, with a high score indicating a higher level of diarrhea. Negative change from Baseline values indicate improvement in diarrhea and positive values indicate worsening of diarrhea.
Time Frame Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
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ITT population with available data.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
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Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 508 509 510
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 1 Number Analyzed 438 participants 444 participants 416 participants
3.8  (25.53) 2.3  (24.94) -0.6  (18.79)
Month 3 Number Analyzed 419 participants 413 participants 395 participants
3.7  (24.99) 3.4  (27.27) -2.4  (18.61)
Month 6 Number Analyzed 373 participants 376 participants 351 participants
8.2  (28.36) 6.0  (27.95) -2.2  (21.19)
Month 12 Number Analyzed 303 participants 299 participants 253 participants
11.8  (31.35) 9.1  (28.74) -2.5  (17.26)
Month 18 Number Analyzed 246 participants 241 participants 178 participants
14.8  (31.20) 10.9  (30.96) -1.7  (17.46)
Discontinuation Visit Number Analyzed 206 participants 261 participants 255 participants
10.8  (29.56) 6.4  (31.38) -0.5  (19.39)
33.Secondary Outcome
Title Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used in clinical research to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Financial Difficulties Scale is scored between 0 and 100, with a high score indicating a higher level of financial difficulties. Negative change from Baseline values indicate improvement in financial difficulties and positive values indicate worsening of financial difficulties.
Time Frame Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
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ITT population with available data.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
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Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 501 504 502
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 1 Number Analyzed 435 participants 441 participants 409 participants
2.1  (21.43) -0.3  (20.59) 0.5  (22.98)
Month 3 Number Analyzed 413 participants 407 participants 388 participants
1.9  (23.09) -0.4  (21.88) 1.9  (21.48)
Month 6 Number Analyzed 370 participants 373 participants 345 participants
1.4  (22.92) -0.3  (21.24) 0.7  (24.57)
Month 12 Number Analyzed 302 participants 299 participants 249 participants
0.4  (23.99) 1.6  (23.28) 1.1  (23.16)
Month 18 Number Analyzed 244 participants 239 participants 174 participants
2.0  (22.23) 1.8  (23.30) 0.4  (21.20)
Discontinuation Visit Number Analyzed 197 participants 255 participants 254 participants
1.9  (27.19) 0.5  (23.84) 5.0  (24.82)
34.Secondary Outcome
Title Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale
Hide Description EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; a higher score indicates more severe disease symptom(s).
Time Frame Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
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ITT population with available data.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
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Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 510 512 511
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 1 Number Analyzed 442 participants 448 participants 421 participants
-4.0  (18.75) -4.1  (19.37) -4.4  (19.04)
Month 3 Number Analyzed 422 participants 418 participants 396 participants
-9.1  (21.66) -10.0  (19.97) -7.0  (20.43)
Month 6 Number Analyzed 375 participants 381 participants 353 participants
-8.8  (20.89) -9.9  (20.94) -7.9  (21.94)
Month 12 Number Analyzed 306 participants 303 participants 254 participants
-7.8  (21.74) -8.7  (20.29) -6.5  (21.58)
Month 18 Number Analyzed 249 participants 243 participants 183 participants
-8.7  (23.50) -6.2  (23.30) -7.9  (21.26)
Discontinuation Visit Number Analyzed 205 participants 266 participants 259 participants
-3.5  (24.82) -4.5  (24.90) -3.7  (23.54)
35.Secondary Outcome
Title Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Side Effects Treatment Scale
Hide Description EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; a higher score represents a more severe overall side effect of treatment.
Time Frame Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
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ITT population with available data.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
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Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity.
Participants ≤ 75 years old received 25 mg lenalidomide (R) PO on days 1 to 21 of each 28-day treatment cycle 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless progressive disease (PD) or intolerable toxicity occurred. Those > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Those with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day (QOD) on days 1-21 of each 28-day cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle for up to 18 cycles unless PD or intolerable toxicity.
Participants received melphalan (M) 0.25 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred. Participants with moderate to severe renal insufficiency received melphalan (M) 0.10-0.125 mg/kg PO daily (QD) on days 1 to 4 of each 42-day cycle plus prednisone (P) at 2 mg/kg PO on days 1 to 4 of each 42-day cycle and thalidomide 100-200 mg PO QD on days 1 to 41 of each 42-day cycle. MPT therapy was given for up to 12 cycles unless PD or intolerable toxicity occurred.
Overall Number of Participants Analyzed 509 511 510
Mean (Standard Deviation)
Unit of Measure: units on a scale
Month 1 Number Analyzed 438 participants 446 participants 418 participants
2.5  (13.72) 4.0  (14.89) 5.6  (15.00)
Month 3 Number Analyzed 421 participants 417 participants 393 participants
1.0  (15.23) 1.2  (14.67) 3.5  (15.40)
Month 6 Number Analyzed 374 participants 378 participants 351 participants
1.7  (15.58) -0.4  (14.39) 2.9  (17.28)
Month 12 Number Analyzed 305 participants 301 participants 254 participants
1.9  (14.49) 1.2  (16.20) 4.7  (17.17)
Month 18 Number Analyzed 247 participants 243 participants 182 participants
2.2  (15.63) 2.3  (17.36) 4.3  (16.37)
Discontinuation Visit Number Analyzed 205 participants 262 participants 258 participants
0.6  (15.85) -1.0  (15.81) 3.8  (16.52)
36.Secondary Outcome
Title Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Future Perspective Scale
Hide Description EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in patients with multiple myeloma. EORTC QLQ-MY20 includes four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used a 4-point scale (from 1 'Not at All' to 4 'Very Much'). Scores were averaged, and transformed to a 0-100 scale; for the future perspective scale, a higher score indicates a better perspective of the future.
Time Frame Cycle 1 Day 1 (Baseline), then Months 1, 3, 6, 12, 18 and Discontinuation visit
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ITT population with available data.
Arm/Group Title Lenalidomide and Low-Dose Dexamethasone (Rd) Lenalidomide and Dexamethasone Rd18 Melphalan + Prednisone + Thalidomide (MPT)
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Participants ≤ 75 years old received 25 mg lenalidomide (R) administered by mouth (PO) on days 1 to 21 of each 28-day cycle plus 40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants > 75 years old received lenalidomide 25 mg PO on the same schedule and frequency plus 20 mg dexamethasone at the same schedule. Participants with moderate renal insufficiency received 10-15 mg lenalidomide (R) PO on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d) PO on days 1, 8, 15, and 22 of a 28-day cycle until disease progression or intolerable toxicity. Participants with severe renal insufficiency received 15 mg lenalidomide (R) PO every other day on days 1-21 of each 28-day treatment cycle and 20-40 mg dexamethasone (d)