Initial Inclusion Criteria:

1. Patients must be considered transplant eligible by the treating physician at time of study entry.
2. Patients must meet the criteria for symptomatic multiple myeloma (Appendix A) prior to initiating systemic anti-myeloma treatment.
3. Age >18 years and ≤ 70 years at the time of enrollment
4. Karnofsky Performance status of ≥ 70%
5. Patients must have > 20% plasma cells in the bone marrow aspirate differential <60 days prior to enrollment. The required bone marrow evaluation will need to be repeated for patients who received more than 1 cycle of anti-myeloma therapy (cortiscosteroid with or without other anti-myeloma agents)
6. Patients must have received < 2 cycles of systemic anti-myeloma therapy.
7. Renal: Creatinine clearance of ≥ 40 mL/min, estimated or calculated.

Initial Exclusion Criteria:

1. Patients with a prior autologous or allogeneic HCT
2. Patients with purely non-secretory MM [absence of a monoclonal protein (M protein) in serum as measured by electrophoresis and immunofixation and the absence of Bence Jones protein in the urine defined by use of conventional electrophoresis and immunofixation techniques and the absence of involved serum free light chain >100 mg/L]. Patients with light chain MM detected in the serum by free light chain assay are eligible.
3. Patients with Plasma Cell Leukemia
4. Patients with High-Risk Multiple Myeloma. High-risk is defined by the presence of any one of the following: deletion of chromosome 13 by conventional cytogenetics, hypodiploidy, abnormality in chromosome 1(1q amplification or 1p deletion), t(4;14), t(14;16), t(14;20) or deletion of 17p by fluorescence in situ hybridization (FISH) or conventional karyotyping; high-risk criteria based on commercially available gene expression profiling (GEP) detected at any time prior to enrollment;
5. Patients with disease progression prior to enrollment (see Section 3.1.2 for disease progression definition).
6. Patients seropositive for the human immunodeficiency virus (HIV).
7. Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure (see Appendix H), 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 will be documented by the investigator as not medically relevant.
8. Patients with active clinically significant autoimmune disease, defined as a history of requiring systemic immunosuppressive therapy and at ongoing risk for potential disease exacerbation. Patients with a history of autoimmune thyroid disease, asthma, or limited skin manifestations are potentially eligible.
9. Patients receiving other investigational immunotherapy or anti-myeloma drugs within 14 days before enrollment.
10. Patients with prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent < 5 years prior to enrollment will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs. Cancer treated with curative intent > 5 years prior to enrollment is allowed.
11. Female patients who are pregnant (positive beta-HCG) or breastfeeding.
12. Females of childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use contraceptive techniques (Appendix D) during the length of lenalidomide maintenance therapy.
13. Patients who have received mid-intensity melphalan (>50 mg IV) as part of prior therapy.
14. Prior organ transplant requiring immunosuppressive therapy.
15. Patients who previously received lenalidomide and have experienced toxicities resulting in treatment discontinuation.
16. Patients who experienced thromboembolic events while on full anticoagulation during prior therapy with lenalidomide or thalidomide.
17. Patients unwilling to take DVT prophylaxis.
18. Patients unable or unwilling to provide informed consent.
19. Patients unable or unwilling to return to the transplant center for their assigned treatments.

Randomization Inclusion Criteria:

1. Patient received transplant < 12 months of enrollment onto BMT CTN 1401.
2. No disease progression since initiation of systemic anti-myeloma therapy as determined within seven days of randomization/enrollment.
3. Received an autologous cell transplant with melphalan 200mg/m^2 with a minimum cell dose of 2x10^6 CD34+ cells/kg (actual body weight).
4. Mucositis and gastrointestinal symptoms resolved, off hyperalimentation and intravenous hydration.
5. No evidence of uncontrolled infection requiring systemic therapy. Patients who completed treatment for an infection but are continuing antibiotics, anti-viral, or anti-fungal therapy for prophylaxis are eligible to continue on protocol.
6. Platelet count ≥75,000/mm^3 (without transfusion in previous 7 days).
7. Absolute neutrophil count (ANC) ≥ 1,500/mm^3 without filgrastim administration within 7 days, or pegfilgrastim within 14 days of measurement.
8. Hepatic: bilirubin < 2x the upper limit of normal and ALT and AST < 2.5x the upper limit of normal. (Patients who have been diagnosed with Gilbert's Disease are allowed to exceed the defined bilirubin value of 2x the upper limit of normal.)
9. Renal: Creatinine clearance of ≥ 40 mL/min, estimated or calculated. Patients with creatinine clearance ≥30 but <40 will be considered with review/approval from the protocol chairs or officer if the cause of renal insufficiency is associated with multiple myeloma.
10. All study participants must be registered into the mandatory Revlimid REMs program, and be willing and able to comply with the requirements.
11. Females of childbearing potential (FCBP) as defined in section 2.7.1.1 must have a negative serum 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)
12. FCBP must either commit to abstain continuously from sexual intercourse or use 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, during therapy, during dose interruptions, and continuing for 4 weeks following discontinuation of lenalidomide.
13. FCBP must agree to ongoing pregnancy testing as required by the RevlimidREMs program.
14. Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy while taking lenalidomide, during dose interruptions and for 28 days after discontinuing lenalidomide.
15. Patients must be willing to receive DVT prophylaxis.