* PRE-REGISTRATION-INCLUSION CRITERIA: * Age \>= 18 years and =\< 80 years. * Patient must have suspected or confirmed newly diagnosed multiple myeloma by International Myeloma Working Group (IMWG) criteria. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1. * Provide informed written consent. * Willing to return to enrolling institution for follow-up during the active treatment phase of the trial. * Willing to provide blood and bone marrow samples for planned research. * Life expectancy \> 6 months. * Able to take aspirin (325 mg) daily as prophylactic anticoagulation. * Note: subjects intolerant to aspirin may use warfarin, novel oral anticoagulants, or low dose molecular weight heparin. * Patients must have monoclonal protein studies (serum free light chain assay, serum immunofixation or serum matrix-assisted laser desorption ionization time-of-flight mass-spectrometry \[MASS-FIX\]) at time of diagnosis before induction therapy initiated and available for review to be enrolled. Note: Patients are allowed to participate in this study if urine electrophoresis immunofixation study was not done at time of diagnosis or cannot be obtained * REGISTRATION-INCLUSION CRITERIA: * High risk myeloma, which is untreated, defined as any two of: * Beta-2 microglobulin \>5.5 * Gain or amplification of chr1q * del17p or monosomy 17 or TP53 mutation (if known) * t(4;14) or t(14;16) * \>= 5% circulating plasma cells * presence of extramedullary disease (does not include bone contiguous disease) * Creatinine clearance \>= 30 mL/min (using Cockroft-Gault equation) (obtained =\< 14 days prior to registration). * Absolute neutrophil count (ANC) \>= 1000/mm\^3 (without the use of growth factors) (obtained =\< 14 days prior to registration). * Platelet count \>= 75000/mm\^3 (obtained =\< 14 days prior to registration). * Hemoglobin \>= 8.0 g/dL. * Total bilirubin =\< 1.5 x upper limit of normal (ULN) (obtained =\< 14 days prior to registration). * Alanine transaminase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN (obtained =\< 14 days prior to registration). * Registration must be completed =\< 30 days after pre-registration. * Patients must not have received more than one cycle of treatment between pre-registration and registration. * All 4 drugs in the study regimen approved by insurance. * Left ventricular ejection fraction (LVEF) \>= 40% =\< 30 days prior to pre-registration