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 eligibility criteria are not allowed within 3 days before study enrollment.
• Total bilirubin ≤ 1.5 mg/dL (If total is elevated check direct and if normal patient is eligible.)
• AST ≤ 3 x institutional upper limit of normal (ULN)
• ALT ≤ 3 x institutional upper limit of normal (ULN)
• Creatinine ≤ 1.5 mg/dL
• WBC ≥2000/μL
• Ability to understand and willingness to sign a 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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 1 year before the screening visit or are surgically sterile. Females of childbearing potential* must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days as required by Revlimid REMS®) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. Females of reproductive potential must agree to follow instructions for method(s) of contraception for the duration of treatment with any study drug(s) plus 5 half-lives of study plus 30 days (duration of ovulatory cycle) for a total of 120 days post treatment completion. Women must not breastfeed. -- A female of childbearing potential is a sexually mature female who:
• Has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or
• Has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time during the preceding 24 consecutive months)
• All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program.
• Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.
• Men must agree to use a latex condom during sexual contact with a female of childbearing potential even if they have had a successful vasectomy during the entire study treatment period and through 154 days after the last dose of study