Carfilzomib, Lenalidomide and Dexamethasone Versus Lenalidomide and Dexamethasone in High- Risk SMM

Inclusion criteria * Patients must have histologically or cytologically confirmed Smoldering Multiple Myeloma based on the 2014 International Myeloma Working Group Criteria(20): * Serum M-protein ≥3.0 g/dl, or urinary monoclonal protein \>500 mg per 24 hours, and/or monoclonal bone marrow plasma cells ≥10-60 % * Absence of CRAB symptoms: * anemia: Hemoglobin \<6.2 mmol/L (10 g/dl) or a hemoglobin value of \>1.2 mmol/L (2 g/dL) below the lower limit of normal * renal failure: serum creatinine \> 2.0 mg/dL or creatinine clearance \< 40 ml/min * hypercalcemia: serum calcium \>0·25 mmol/L (\>1 mg/dL) higher than the upper limit of normal or \>2·75 mmol/L (\>11 mg/dL) * Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT * Absence of myeloma defining events: * Involved/uninvolved serum free light chain ratio ≥100 with involved free light-chain concentration ≥10 mg/dl * Presence of 2 or more focal lesions by MRI (2 of which at least 5 mm) * Clonal bone marrow plasma cell percentage ≥60% * Patients must have high risk Smoldering Multiple Myeloma based on the Mayo Clinic and/or the PETHEMA criteria: * 3 factors of Mayo Clinic criteria: * Bone marrow plasma cells ≥10 % * Serum M-protein ≥ 3 g/dl * Serum free light-chain ratio \<0.125 or \>8 * And/or 2 factors of PETHEMA criteria: * Of the plasma cell population ≥95% abnormal plasma cells (presence or absence of CD38, CD56, CD19 and/or CD45) * Immunoparesis, a reduction (below the lower normal limit) in…