Ixazomib (MLN9708) and Dexamethasone in High Risk Smoldering Multiple Myeloma: A Clinical and Correlative Pilot Study

Inclusion Criteria: * Patients must have histologically or cytologically confirmed Smoldering Multiple Myeloma confirmed by Department of Pathology, based on the International Myeloma Working Group Criteria * Serum M-protein ≥3 g/dl and/or bone marrow plasma cells ≥10 %, * Absence of anemia attributed to the plasma cell disorder\*: Hemoglobin \>10 g/dl or not more than 2g/dL below the lower limit of normal * Absence of renal failure attributed to the plasma cell disorder\*: calculated creatinine clearance (according to Cockcroft-Gault method, MDRD, or CKD-EPI formulae) \> 30 mL/min (or alternatively based on standard creatinine level criteria of 2 mg/dl) * Absence of hypercalcemia attributed to the plasma cell disorder\* (: Ca \< 10.5 mg/dl or ≤ 2.5 mmol/L * Absence of lytic bone lesion * Absence of Clonal bone marrow plasma cell percentage ≥60% * Absence of Involved: uninvolved serum free light chain ratio ≥100 * Absence \>1 focal lesions on MRI studies \* To be determined based on clinical and laboratory assessment by the primary oncologist * "High-risk SMM" per Mayo Clinic or Spanish PETHEMA criteria * Measurable disease within the past 4 weeks defined by any one of the following * Serum monoclonal protein ≥ 1.0 g/dl * Urine monoclonal protein \>200 mg/24 hour * Serum immunoglobulin free light chain \>10 mg/dL AND abnormal kappa/lambda ratio (reference 0.26-1.65) * Age ≥18 years * ECOG performance status 0, 1, or 2. * Ability to give informed consent. * Pa…