Subjects up to the age of 65 years with newly diagnosed multiple myeloma requiring treatment are eligible. Minimal pretreatment (2 cycles of chemotherapy; local irradiation; surgery) is permitted. After enrollment, patients are to receive four cycles of RAD induction treatment: a combination of lenalidomide (Revlimid), adriamycin, and dexamethasone. If at least a minimal response is achieved to RAD, they will undergo chemomobilization (cyclophosphamide, etoposide) of peripheral blood stem cells and one uniform cycle of high-dose melphalan chemotherapy followed by a first stem cell transplant. If any of the high-risk features (such as elevated beta 2-microglobulin, adverse cytogenetic factors, elevated LDH, Ig A isotype) were present at diagnosis, patients will be allocated to a consolidative allogeneic transplant following dose-reduced conditioning. If no appropriate donor is available, the patient does not consent or lacks of high-risk features a second autograft following high-dose melphalan will be delivered. All patients will proceed to lenalidomide maintenance (one year) following hematopoietic reconstitution.

Inclusion Criteria:

• Written informed consent
• Newly diagnosed multiple myeloma
• Maximum of one prior systemic therapy (2 cycles)
• Presence of CRAB criteria
• Measurable disease parameters
• Left ventricular ejection fraction at least 55%
• DLCO of at least 60%
• Adequate bone marrow function
• Use of adequate contraception for female subjects with childbearing potential and all male subjects
• Eligible for autologous and allogeneic stem cell transplantation
• Bone marrow baseline sample evaluable for interphase cytogenetics

Exclusion Criteria:

• Any serious medical conditions preventing the subject from written informed consent
• Progressive disease (PD) to any initial treatment
• Pregnant or lactating females
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data
• Use of any other experimental drug or therapy within 28 days of baseline
• Preexisting neuropathy of ≥ grade 2 severity
• Known hypersensitivity to thalidomide
• Any prior use of lenalidomide
• Positive for HIV or infectious hepatitis, type A, B or C after serologic testing
• Serum creatinine despite induction therapy ≥ 2.0 mg/dL