Elotuzumab and Lenalidomide After Stem Cell Transplant in Treating Patients With Newly Diagnosed Multiple Myeloma

Prior treatment

• Major surgery within 14 days before the first dose of study drug
• Radiotherapy within 14 days before enrollment
• Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal (GI) procedure that could interfere with the oral absorption or tolerance of treatment
• Infection requiring systemic IV antibiotic therapy within 7 days before cycle 1 day 1 of therapy
• Failure to have fully recovered (i.e., =\< grade 1 toxicity) from the effects of prior chemotherapy regardless of the interval since last treatment
• Co-morbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

Other illness

• Known active hepatitis B virus hepatitis, or known active hepatitis C virus
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations

Other

• Known active central nervous system involvement
• Female subject is pregnant or lactating

• Patients must have undergone autologous stem cell transplantation, within 18 months of initiation of induction therapy for newly diagnosed myeloma
• Time to initiation of maintenance therapy: patients may start maintenance therapy as early as 60 days post-transplant and up to 210 days post-transplant; as long as they meet the following criteria:
• Platelet count \>= 100,000/mm\^3
• Neutrophil count \>= 1000/mm\^3 (no growth factors within 5 days)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN
• Creatinine \< 2.5 mg/dl
• Recovered (i.e., =\< grade 1 toxicity) from the reversible effects of autologous stem cell transplant
• Patients whose primary therapy was changed due to suboptimal response or toxicity will be eligible, however no more than 2 regimens will be allowed prior to ASCT
• Patients must have an Eastern Cooperative Oncology Group (ECOG) status of 0 to 2
• 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
• Female patients who: are postmenopausal for at least 24 months before the screening visit, OR; are surgically sterile, OR; if they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, 28 days prior to starting study drug, during study treatment and for 28 days after the last dose of study treatment, OR agree to completely abstain from heterosexual intercourse; male patients, even if surgically sterilized (i.e., status post vasectomy), who: agree to practice effective barrier contraception during the entire study treatment period and through 28 days after the last dose of study treatment, OR; agree to completely abstain from heterosexual intercourse