Combination of Revlimid, Melphalan and Dexamethasone as First Line Treatment for Multiple Myeloma

Inclusion Criteria: * Newly Diagnosed multiple myeloma, ISS stage I-III requiring therapy: Serum M-protein ≥1 gm/dL (≥10 gm/L), Urine M-protein ≥200 mg/24 hr, Serum FLC assay: involved FLC ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal * Previously untreated except prior treatment with corticosteroid less than one full cycle of pulsed dose dexamethasone (40 mg daily days 1-4, 9-12, and 17-20) or equivalent is allowed. Concomitant administration of IV bisphosphonates, Zometa (zoledronic acid, up to 4 mg IVSS over 30 minutes every four weeks) or Aredia (alendronate, up to 90 mg IVSS over 4 hours every four weeks), for prophylaxis against skeletal complications due to lytic bone disease or for acute management of hypercalcemia is allowed. Concomitant external beam radiation therapy for local management of lytic bone disease is allowed. * Age ≥ 18 years old * Life expectancy ≥ 12 weeks * Eastern Cooperative Oncology Group (ECOG) Performance Status will be employed. ECOG 0-2 accepted. * WBC ≥ 3.0 X 103/ µL, ANC ≥ 1.5 X 103/ µl, Hgb ≥ 8.0 gm/ dL, Plt ≥ 75 X 103/ µl, Serum Creatinine ≤ 2.0 mg/ dL * Ability to understand and the willingness to sign a written informed consent document. * All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®. * 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 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. See Appendix A: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods. * 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: * Prior therapy with Revlimid®, Thalomid (thalidomide), Velcade (bortezomib), Alkeran (melphalan) excluded. Prior therapy with corticosteroid allowed as defined in inclusion criteria. * No prior or concurrent treatment with an investigational agent. * Active Hepatitis B or C excluded, New York Heart Association grade III/IV congestive heart failure excluded, History of bleeding disorder excluded, History of platelet function disorder, History of deep vein thrombosis or other thromboembolic event excluded * Prior history of allergic reaction to IMiD™ compounds (Thalidomide, Lenalidomide) excluded. * Concomitant treatment with nonsteroidal antiinflammatory drugs (NSAIDs)(with the exception of aspirin) or other nephrotoxic agents is excluded. * Serum creatinine \> 2.0 mg/ dL is excluded * Pregnancy and breastfeeding excluded * Known HIV+ patients are excluded. * Other active hematologic or solid tumor or history of such disease requiring therapy of any form within five years of screening is excluded.