REsponse Adapted Combination Therapy Approaches for High-Risk Multiple Myeloma (REACH)
This phase II trial test whether combination chemotherapy works to improve blood test results in patients with high-risk multiple myeloma. Chemotherapy drugs, such as carfilzomib, daratumumab, lenalidomide, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial may help determine if patients who have a small amount of cancer left after the initial treatment, called minimal residual disease, will benefit from the drug combination.
• 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