Based on the need to improve outcomes post second autologous stem cell transplant (ASCT) for multiple myeloma (MM) and the benefits seen of maintenance treatment following initial ASCT, the natural next step is to evaluate maintenance/continuation therapy following second ASCT.

Pomalidomide is active against MM cells refractory to both bortezomib and lenalidomide, making it an ideal choice for continuation therapy following second ASCT. Adding elotuzumab may increase efficacy and also the durability of responses which is essential to improving outcomes following second ASCT.

Inclusion Criteria:

• Histologically confirmed diagnosis of multiple myeloma.

• Received prior autologous stem cell transplantation as first line therapy for multiple myeloma with subsequent disease relapse/progression.

• Failed 1 or 2 lines of treatment for multiple myeloma. A line of treatment includes all therapy including induction, transplant, and maintenance administered in a sequence in the absence of relapse/progression. Once relapse/progression occurs and subsequently the anti-myeloma treatment is changed, a new line of treatment has begun. Local radiation or corticosteroids will not be considered treatment for multiple myeloma.

• Received 2 to 6 cycles of induction therapy per standard of care prior to 2nd autologous stem cell transplantation

• Received standard of care melphalan conditioning for 2nd autologous stem cell transplantation, is currently Day +80 to +120 following transplant, and is responding to therapy (partial response or better as compared to pre-induction assessment.

• All US study participants must be registered into the mandatory POMALYST REMS® program and be willing and able to comply with the requirements of the POMALYST REMS® program. For Canadian sites, patients will followed according to the Pomalidomide pregnancy prevention program

• Females of reproductive potential within the US must agree to adhere to the scheduled pregnancy testing as required in the POMALYST REMS® program. For Canadian sites, patients will followed according to the Pomalidomide pregnancy prevention program

• At least 18 and no more than 75 years of age at enrollment.

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

• Normal bone marrow and organ function as defined as ALL of the following:

  • Absolute neutrophil count ≥ 1000/mm^3
  • Platelets ≥ 75,000/mm^3 (transfusions not permitted within 7 days of screening)
  • Total bilirubin ≤ 2.0 x institutional upper limit of normal (IULN)
  • AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
  • Creatinine clearance ≥ 15 mL/min

• Females of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry through Day +100 visit. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.

• Able to understand and willing to sign an Institutional Review Board (IRB) approved written informed consent document.

Exclusion Criteria:

• Refractory to elotuzumab and/or pomalidomide, defined as progressive disease or clinical relapse on therapy or within 60 days following completion of therapy. Prior exposure to elotuzumab and/or pomalidomide is allowed as long as patient is not refractory to these agents.
• More than one prior transplant prior to study entry with the exception of tandem transplantation. Tandem transplantation is defined as two autologous stem cell transplants that occur within 9 months of one another, and the patient did not have disease progression in the period between the two transplants.
• Presence of peripheral neuropathy ≥ grade 3 based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 4.0
• History of plasma cell leukemia or MM central nervous system (CNS) involvement.
• Receiving renal replacement therapy, hemodialysis, or peritoneal dialysis.
• Diagnosed with another concurrent malignancy requiring treatment.
• Known HIV or active hepatitis A, B, or C. Antidoby testing not required for screening
• Known hypersensitivity to pomalidomide, dexamethasone, or any excipients in elotuzumab, formulation, or recombinant protein
• Receiving any other investigational agents within 14 days prior to enrollment.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• Pregnant and/or breastfeeding. Females of childbearing potential must have two negative pregnancy tests. The first test should be performed within 10-14 days of study entry, and the second test within 24 hours prior to prescribing pomalidomide.