Isatuximab in Combination With Rd Compared to Rd in Elderly Patients (Aged ≥70 Years) With NDMM

Inclusion Criteria: * Age ≥ 70 years * Able to provide written informed consent in accordance with federal, local, and institutional guidelines * Patients must have newly diagnosed, symptomatic multiple myeloma with evidence of measurable disease (assessed within 21 days prior to randomization) * Serum M protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis and/or * Urine M protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis and/or * In subjects without detectable serum or urine M-protein, serum free light chain (SFLC) ≥100 mg/L (involved light chain) and an abnormal FLC ratio * No prior treatment for multiple myeloma * Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2 * Patients at cardiac risk (NYHA \>ll) or pre-existing coronary heart disease, or any other clinically relevant cardiac complication) should be scheduled for a baseline ECHO and can only be included if the LVEF is \>40% * Adequate organ and bone marrow function within the 21 days prior to randomization defined by: * Bilirubin \< 2 times the upper limit of normal (ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 times the ULN * absolute neutrophil count (ANC) ≥ 750/mm3 (growth factor support for max 3 days allowed to achieve this value) * Hemoglobin \>8.0 g/dL (Use of erythropoietic stimulating factors and red blood cell \[RBC\] transfusion per institutional guidelines is allowed, however the most recent RBC transfusion may not have been done within 7 days prior to obtaining screening hemoglobin.) * Platelet count \>50,000/mm3 * Calculated or measured creatinine clearance (CrCl) of ≥30 mL/min; Calculation should be based on the MDRD formula (age, gender, black/non- black, weight, height) Exclusion Criteria: * ECOG status \>2 * Patients unlikely to tolerate Rd * Waldenström macroglobulinemia * POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) * Plasma cell leukemia (\> 2.0 x 10\^9/L circulating plasma cells by standard differential) * Myelodysplastic syndrome * Smoldering Myeloma and MGUS * Second malignancy within the past 5 years except: * Adequately treated basal cell or squamous cell skin cancer * Carcinoma in situ of the cervix * Prostate cancer ≤ Gleason score 6 with stable prostate-specific antigen (PSA over 12 months) * Ductal breast carcinoma in situ with full surgical resection (i.e., negative margins) * Treated medullary or papillary thyroid cancer * Other tumors with low risk of recurrence/metastases and/or early stage R0 surgery * History of or current amyloidosis * Glucocorticoid therapy within the 14 days prior to randomization that exceeds an accumulated dose of 160 mg dexamethasone or 1000 mg prednisone * Extended field radio therapy (more than 3 fields) within the 21 days prior to randomization * Contraindication to isatuximab, dexamethasone, lenalidomide or any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs * Active congestive heart failure (New York Heart Association \[NYHA\] Class III or IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, acute diffuse infiltrative pulmonary disease, pericardial disease, or myocardial infarction within 4 months prior to enrolment * Active infection within the 14 days prior to randomization requiring systemic antibiotics and/or antiviral therapy * Uncontrolled hypertension or uncontrolled diabetes despite medication * Significant neuropathy (Grade 2 with pain or Grade 3 or higher) within the 14 days prior to randomization * Known cirrhosis * Known human immunodeficiency virus (HIV) seropositivity or active hepatitis C or hepatitis B infection (subjects with past hepatitis B virus \[HBV\] infection or resolved HBV infection defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen \[anti HBc\] antibody test are eligible; subjects positive for hepatitis C virus \[HCV\] antibody are eligible only if polymerase chain reaction \[PCR\] is negative for HCV RNA.) * Participation in another interventional study within the 28 days prior to randomization * Major surgery (except kyphoplasty) within the 28 days prior to randomization * Any other clinically significant medical disease or social condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent, be compliant with study procedures, or provide accurate information.