Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form.
2. Age 18 years or older at the time of signing the informed consent form.
3. Able to adhere to the study visit schedule and other protocol requirements.

4. Multiple myeloma diagnosed according to the following standard criteria (all three criteria must be met):

   • Monoclonal plasma cells in bone marrow ≥10% and/or presence of biopsy-proven plasmacytoma
   • Monoclonal protein present in serum and/or urine Myeloma-related organ dysfunction (1 or more) (C) Calcium elevation in blood (serum calcium >10.5 mg/L or ULN) (R) Renal insufficiency (SCr >2 mg/dL) (A) Anemia (hemoglobin <10 g/dL or 2g <normal) (B) Lytic bone lesions or osteoporosis
5. Subjects must have measurable disease requiring systemic therapy.

6. High risk multiple myeloma defined by the presence of one or more of the following:

   • Deletion of chromosome 13 by metaphase analysis (standard cytogenetics) only
   • deletion of 17p13 (p53) by FISH or metaphase analysis (standard cytogenetics)
   • t(4;14) by FISH analysis
   • t(14;16) by FISH analysis
   • t(8;14) by FISH analysis
   • t(14;20) by FISH analysis
   • hypodiploidy detected by FISH or metaphase analysis (standard cytogenetics)
   • any complex cytogenetic abnormality detected by metaphase analysis (standard cytogenetics), with the exception of hyperdiploidy
7. Subject must not have been treated previously with any systemic therapy or radiation therapy active against myeloma lasting more than 4 weeks duration.
8. Prior to enrollment at least 7 days must have elapsed since the date of the last radiation or systemic treatment against myeloma.
9. ECOG performance status of less than or equal to 2 at study entry.(See Appendix 15.1)
10. All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
11. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) 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 4 weeks before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree not to father a child and agree to use a latex*condom even if he has had a successful vasectomy, if his partner is of child bearing potential.
12. Disease free of prior malignancies for at least 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast
13. Able to take 325 mg aspirin daily as prophylactic anticoagulation for the duration of protocol related therapy to include induction and maintenance. Other appropriate daily anticoagulation, such as warfarin or low molecular weight heparin, may be used at physician discretion. Lenalidomide increases the risk of thrombotic events in patients who are at high risk or with a history a thrombosis, in particular when combined with other drugs known to cause thrombosis. When lenalidomide is combined with other agents such as steroids (e.g. dexamethasone, prednisone), anthracyclines (Doxil, Adriamycin) and erythropoietin the risk of thrombosis is increased.
14. Patients should receive concomitant therapy with bisphosphonates if bony lesions are present at time of enrollment.