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 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.