Elotuzumab and Lenalidomide in Treating Patients with Recurrent or Progressive Multiple Myeloma

Inclusion Criteria

• Patients with multiple myeloma who demonstrate evidence of serologic relapse/progression while on lenalidomide maintenance given as part of first line therapy (including upfront high-dose chemotherapy followed by autologous hematopoietic cell transplantation [HCT]) without symptomatic relapse/progression. * Lenalidomide maintenance is defined as single agent lenalidomide therapy of any doses up to 10 mg PO daily for 14-28 days (28-day cycle). Relapse/progression is defined as increase of 25% from lowest confirmed response value in one or more of the following criteria: ** Serum M –protein (absolute increase must be >= 0.5g/dl) ** Serum M-protein increase > 1g/dl, if the lowest M component was > 5 g/dl ** Urine M –protein (absolute increase must be > 200 mg in 24 hours) ** In patients without measurable serum and urine M-protein levels, the difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be > 10 mg/dl) * For patients relapsing from complete remission, relapse is defined as: reappearance of serum or serum M-protein by immunofixation or electrophoresis
• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
• Measurable disease with at least 1 of the following assessed within 21 days prior to cycle 1 day 1: * Serum M-protein >= 0.5 g/dL * Urine M-protein >= 200 mg/24 hour * In subjects without measurable serum or urine M-protein, serum free light chain (SFLC) > 10 mg/dL (involved light chain) and an abnormal serum kappa lambda ratio
• Absolute neutrophil count (ANC) >= 1 x 10^9/L (within 28 days prior to cycle 1, day 1)
• Hemoglobin >= 10 g/dl (within 28 days prior to cycle 1, day 1)
• Platelet count >= 75,000/mm^3 (within 28 days prior to cycle 1, day 1)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) (within 28 days prior to cycle 1, day 1)
• Serum bilirubin =< 1.5 x ULN (within 28 days prior to cycle 1, day 1)
• Serum creatinine clearance >= 50 ml/min (within 28 days prior to cycle 1, day 1)

Exclusion Criteria

• Prior elotuzumab
• Patients with clinical relapse/progression as per the International Myeloma Working Group (IMWG) uniform criteria defined as one or more of the following criteria: * Development of new soft tissue plasmacytomas or bone lesions (osteoporotic fractures do not constitute progression) * Definite increase in the size of existing plasmacytomas or bone lesions. A definite increase is defined as a 50% (and >= 1 cm) increase as measured serially of the measurable lesion * Hypercalcemia (> 11 mg/dL) * Decrease in hemoglobin of >= 2 g/dL not related to therapy or other non-myeloma-related conditions * Rise in serum creatinine by 2 mg/dL or more from the start of the therapy and attributable to myeloma * Hyperviscosity related to serum paraprotein
• Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not using an effective method of birth control. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential must have a negative serum pregnancy testing within 7 days prior to the administration of drug
• Male patients whose sexual partners are WOCBP not using effective birth control
• Patients with a prior malignancy within the last 5 years (except for skin basal or squamous cell carcinoma, or in situ cancer of the cervix)
• Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required
• Patients with a diagnosis of POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or plasma cell leukemia (> 2.0 x 10^9/L circulating plasma cells by standard differential)