A Phase II Trial If Nivolumab, Lenalidomide and Dexamethasone in High Risk Smoldering Myeloma

Inclusion Criteria: * Age 18 years. * Must meet criteria of high risk smoldering MM based on the criteria described below: \-- Definition of high-risk SMM: \--- Bone marrow clonal plasma cells ≥10% and ≤60% and any one or more of the following: * Serum M protein ≥3.0g/dL (IgA, IgG, IgM, or IgD) * IgA SMM * Immunoparesis with reduction of two uninvolved immunoglobulin isotypes * Serum involved/uninvolved free light chain ratio ≥8 (but less than 100) \----- Free Light Chain Smoldering Myeloma patients as defined in section 2.4 are not excluded * Progressive increase in M protein level (Evolving type of SMM) \----- Increase in serum monoclonal protein by ≥10% on two successive evaluations within a 6 month period * 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 one focal lesion with increased uptake without underlying osteolytic bone destruction * Urine monoclonal light chain excretion ≥500 mg/24 hours * ECOG Performance Status (PS) 0, 1, or 2 (Appendix A) * The following laboratory values obtained 21 days prior to registration and confirmed prior to the first dose of study drug: * ANC ≥1000/ µL * PLT ≥ 50,000/µL. Platelet transfusions to help patients meet eligib…