E-PRISM: Phase II Trial of Elotuzumab Lenalidomide and Dexamethasone in High-Risk Smoldering Multiple Myeloma

Inclusion Criteria: * Age ≥ 18 years * Must have smoldering myeloma with high risk markers based on the Mayo OR the Spanish criteria as described below * \>10% plasma cells in the bone marrow and any one or more of the following: * Serum M protein of 3 g/dL or greater * IgA SMM * Immunoparesis with reduction of two uninvolved immunoglobulin isotypes * Serum involved/uninvolved free light chain ratio ≥8 (but less than 100) * Progressive increase in M protein level (Evolving type of SMM)† * Bone marrow clonal plasma cells 50-60% * Abnormal plasma cell immunophenotype (≥95% of bone marrow plasma cells are clonal) and reduction of one or more uninvolved immunoglobulin isotypes * t (4;14) or del 17p or 1q gain * Increased circulating plasma cells * MRI with diffuse abnormalities or 1 focal lesion * PET-CT with focal lesion with increased uptake without underlying osteolytic bone destruction † Increase in serum monoclonal protein by ≥25% on two successive evaluations within a 6 month period * No evidence of CRAB (see below for details) criteria or new criteria of active multiple myeloma which including the following: * Increased calcium levels (corrected serum calcium \>0.25 mmol/dL above the upper limit of normal or \>.275 mmol/dL) * Renal insufficiency (attributable to myeloma) * Anemia (Hb 2g/dL below the lower limit of normal or \<10g/dL) * Bone lesions (lytic lesions or generalized osteoporosis with compression fractures) * No evidence of the…