Inclusion Criteria:

Multiple Myeloma Diagnosis: Subject was previously diagnosed with multiple myeloma based on standard diagnostic criteria or by the new International Myeloma Foundation 2003 Diagnostic Criteria:

Standard Criteria

Major criteria:

1. Plasmacytomas on tissue biopsy.
2. Bone marrow plasmacytosis (>30% plasma cells). 3 Monoclonal immunoglobulin spike on serum electrophoresis immunoglobulin G (IgG) >3.5 g/dL or immunoglobulin A (IgA) >2.0 g/dL; kappa or lambda light chain excretion >1 g/day on 24 hour urine protein electrophoresis.

Minor criteria:

1. Bone marrow plasmacytosis (10 to 30% plasma cells)
2. Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria
3. Lytic bone lesions
4. Normal IgM <50 mg/dL, IgA <100 mg/dL or IgG <600 mg/dL.

Any of the following sets of criteria will confirm the diagnosis of multiple myeloma:

• Any two of the major criteria.
• Major criterion 1 plus minor criterion b, c or d.
• Major criterion 3 plus minor criterion a or c.
• Minor criteria a, b and c or a, b and d.

• Patient must not have been previously treated with any prior systemic therapy for the treatment of multiple myeloma.

  • Prior treatment of hypercalcemia or spinal cord compression with corticosteroids does not disqualify the patient (the dose should not exceed the equivalent of 160 mg of dexamethasone in a 2 week period).
  • Bisphosphonates are permitted
• Patients treated with local radiotherapy with or without concomitant exposure to steroids, for pain control or management of cord/nerve root compression, are eligible. One week must have lapsed since last date of radiotherapy, which is recommended to be a limited field. Patients who require concurrent radiotherapy should have entry to the protocol deferred until the radiotherapy is completed and one week have passed since the last date of therapy.
• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL 10 - 14 days prior to therapy and repeated again within 24 hours of prescribing lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. See Appendix IX: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods,.
• Age ≥ 18 years at the time of signing Informed Consent.
• All necessary baseline studies for determining eligibility must be obtained within 21 days prior to enrollment.
• Subject has a Karnofsky performance status of ≥ 60. (Appendix II, Section 8.2)
• Subject must be able to adhere to the study visit schedule and other protocol requirements.
• All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
• Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).

Exclusion Criteria:

A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).

• Patient has ≥ Grade 2 peripheral neuropathy on clinical examination within 14 days before enrollment.
• Renal insufficiency (serum creatinine levels > 2.5 mg/dL).
• Subjects with evidence of mucosal or internal bleeding and/or platelet refractory (i.e., unable to maintain a platelet count ≥ 50,000 cells/mm3).
• Subjects with an absolute neutrophil count (ANC) < 1000 cells/mm3. Growth factors may not be used to meet ANC eligibility criteria.
• Subjects with a hemoglobin < 8.0 g/dL.
• AST (SGOT and ALT (SGPT) > 2 x ULN
• Concomitant therapy medications that include corticosteroids (except as indicated in inclusion criteria).
• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
• Clinically relevant active infection requiring intravenous antibiotics
• Serious co-morbid medical conditions such as chronic obstructive or chronic restrictive pulmonary disease, and cirrhosis.
• Any condition, including laboratory abnormalities, that in the opinion of the Investigator places the subject at unacceptable risk if he/she were to participate in the study.
• Prior malignancy (within the last 3 years) except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer or if the expected survival from other malignancy is greater than 90% at 5 years
• Female subject is pregnant or breast-feeding.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Uncontrolled diabetes mellitus (Fasting Blood Sugar > 400 despite medical treatment)
• Hypersensitivity to acyclovir or similar anti-viral drug
• Known history of POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes).
• Known HIV infection
• Known active hepatitis B or C viral infection