Less Doses of Daratumumab Are Adequate to Achieve Response in Newly Diagnosed Multiple Myeloma

The goal of this clinical trial is to evaluate whether a modified (less frequent) dosing schedule of daratumumab, when added to standard VRd therapy, can be an effective induction regimen for treating newly diagnosed multiple myeloma (NDMM). The main questions it aims to answer are: 1. Does the modified (less frequent) daratumumab dosing regimen increase the rate of MRD (minimal residual disease) negativity after 4 cycles of induction therapy (as compared to standard VRd therapy)? 2. Is the modified less-frequent dosing schedule safe and does it achieve adequate drug levels 3. What is the clinical response of patients to the treatment? Treatment regimen Daratumumab (Dara), Bortezomib, Lenalidomide, and Dexamethasone will be given together for four cycles of induction therapy Duration of each cycle will be 28 days 1. Daratumumab will be given at standard dose of 16mg/kg - Day 1, 15, 29, 50, 71, and 92 (First three doses every 2 weeks, followed by the next three doses every 3 weeks). This will be given intravenously in saline 2. Bortezomib: 1.3 mg/m2 - Given once weekly subcutaneously (similar to insulin) 3. Lenalidomide: 15-25 mg orally for 21 days, followed by a 7-day gap. 4. Dexamethasone: 40mg given once weekly Response Assessment * Response assessment - A bone marrow test will be done within two weeks of end of cycle 4 in order to assess the cancer burden via a special test called MRD (minimal residual disease) in the bone marrow. * Blood tests will be performed to assess your response to treatment (serum protein electrophoresis, immunofixation electrophoresis and serum free light chain assay) after cycle 2 (between day 51-day 56) and cycle 4 (between 107-112). These blood tests are routinely done for all myeloma patients during their treatment to assess response.

Inclusion Criteria 1. Newly diagnosed multiple myeloma 2. ECOG performance status 0-2 3. Age ≥18 years of age 4. Acceptable liver functions, as specified below: Total bilirubin \=5% circulating plasma cells in peripheral blood), AL Amyloidosis, POEMS syndrome 2. Patients with symptomatic central nervous system involvement (as per assessing clinician) 3. Patients with symptomatic obstructive airway disease, as per assessing clinician 4. New York Heart Association (NYHA) Class III or IV cardiac disease, or left ventricular ejection fraction \