Lenalidomide or Observation in Treating Patients With Asymptomatic High-Risk Smoldering Multiple Myeloma

Inclusion Criteria:

• Patients must be diagnosed with asymptomatic high-risk smoldering multiple myeloma (SMM) within the past 12 months, as confirmed by both of the following:

  • Bone marrow plasmacytosis with >= 10% plasma cells or sheet of plasma cells which must be obtained by bone marrow aspiration and/or biopsy within 4 weeks prior to randomization
  • Abnormal serum free-light chain (FLC) ratio (< 0.125 or > 8.0) by serum FLC assay; FLC assay must be performed within 28 days of randomization
• Measurable monoclonal protein in the serum >= 1.0 g/dL or urine >= 200 mg/24 hrs
• No lytic lesions on skeletal surveys and no hypercalcemia (i.e., >= 11 mg/dL)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count (ANC) > 1,500/mm³
• Platelet count > 100,000/mm³
• Hemoglobin > 11 g/dL
• Creatinine clearance > 30 mL/min
• Bilirubin < 1.5 mg/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 times upper limit of normal
• More than 6 months since active, uncontrolled seizure disorder
• Willing to take some form of anti-coagulation as prophylaxis if there is a history of or concurrent deep vein thrombosis or pulmonary embolism
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use 2 effective methods of contraception for ≥ 28 days before, during, and ≥ 28 days after completion of study therapy
• Prior malignancy allowed provided treatment of curative intent was delivered and disease-free for time period considered appropriate for the specific cancer

• Human immunodeficiency virus (HIV)-positive patients allowed provided the following criteria are met:

  • CD4 cell count >= 350/mm³
  • No history of acquired immunodeficiency syndrome (AIDS)-related illness

• No uncontrolled intercurrent illness including any of the following:

  • Uncontrolled hypertension
  • Symptomatic congestive heart failure
  • Unstable angina
  • Uncontrolled cardiac arrhythmia
  • Uncontrolled psychiatric illness or social situation that would limit compliance with the study
  • Prior Stevens Johnson Syndrome
• No peripheral neuropathy >= grade 2
• No active uncontrolled infection
• No New York Heart Association (NYHA) class III or IV heart failure
• No prior or concurrent systemic therapy or radiotherapy for MM
• No prior or concurrent erythropoietin

• No prior glucocorticosteroid for MM

  • Prior systemic glucocorticosteroid for non-malignant disorders allowed (prednisone equivalent ≤ 10 mg/day)
  • Prior or concurrent topical or localized glucocorticosteroid to treat non-malignant comorbid disorders allowed

• No concurrent bisphosphonates

  • Prior bisphosphonates or once-a-year intravenous bisphosphonate for osteoporosis allowed
• No concurrent zidovudine or stavudine for HIV-positive patients
• No concurrent chemotherapy including cyclophosphamide and stem cell mobilization