Selinexor, Daratumumab, Carfilzomib and Dexamethasone for the Treatment of High-Risk, Recurrent or Refractory Multiple Myeloma

Inclusion Criteria

• •Age \>= 18 years
• •Patients must have a documented history of relapsed or relapsed/refractory MM as defined by International Myeloma Working Group (IMWG) criteria (Rajkumar et al., 2014)
• •* Patients must be selinexor and carfilzomib sensitive
• •* Prior daratumumab exposure is allowed, provided that it has been 6 months or more from the time of cycle 1 day 1 (C1D1) of protocol therapy
• •High risk disease defined as 1 or more of the following:
• •* High risk cytogenetics (any of the following)
• •* t(4;14), t(14;16), t(14;20)
• •* del(17p)
• •* del(1p)
• •* Gain 1q (\>= 3 copies)
• •* Lactate dehydrogenase (LDH) \> upper limit of normal at relapse
• •* International Staging System (ISS) stage 3 disease at relapse
• •* Extramedullary disease at diagnosis or relapse
• •* \>= 5% circulating plasma cells at diagnosis or relapse
• •* High risk by gene expression profiling, if known, at diagnosis or relapse
• •* Early relapse with first-line therapy
• •* =\< 18 months from cycle 1 day 1 for patients not undergoing autologous stem cell transplant (ASCT)
• •* =\< 36 months from cycle 1 day 1 for patients undergoing ASCT and post-ASCT maintenance
• •Measurable disease
• •1-3 prior lines of therapy
• •Eastern Cooperative Oncology Group (ECOG) performance status (PS) =\< 2 (Form is available on the Academic and Community Cancer Research United \[ACCRU\] website)
• •Patients must have evidence of adequate bone marrow reserves, as defined by the following:
• •* Absolute neutrophil count (ANC) \>= 1,000 cells/mm\^3 without filgrastim or its equivalent within 1 week of the initiation of treatment or pegfilgrastim or its equivalent within 2 weeks of the initiation of treatment
• •* Platelet count of \>= 100,000 cells/mm\^3 for patients who have bone marrow plasmacytosis of \< 50%, or \>= 50,000 cells/mm\^3 for patients who have bone marrow plasmacytosis of \> 50%, both without platelet transfusion support within 1 week of the initiation of treatment or the use of TPO mimetics
• •* NOTE: If your site laboratory reports use different units of measurements than what is required by the protocol eligibility requirements, please use the "Lab Test Unit Conversion Worksheet" available on the ACCRU website under "General Forms"
• •Total bilirubin =\< 2.0 times the upper limit of the institutional normal values except in subjects with congenital bilirubinemia, such as Gilbert syndrome (in which case a direct bilirubin =\< 1.5 x upper limit of normal \[ULN\] is required)
• •Total aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 times the upper limit of the institutional normal values
• •Patients must have adequate cardiac function defined as left ventricular ejection fraction (LVEF) \>= 45% by echocardiogram, magnetic resonance imaging (MRI) or multigated acquisition (MUGA) scan
• •For those with symptomatic pulmonary disease (e.g. chronic obstructive pulmonary disease \[COPD\], asthma) or other signs/symptoms of pulmonary disease, adequate pulmonary function as defined by a forced expiratory volume in one second (FEV1) \>= 50% of predicted and diffusing capacity for carbon monoxide (DLCO)/alveolar volume (VA) \>= 50% of predicted within 28 days prior to day 1 of treatment
• •* Note: Baseline pulmonary function tests are only required on an as needed basis
• •Patients must have evidence of adequate renal function, as defined by the following: creatinine clearance (CrCl) \>= 30 mL/min., as measured by a 24-hour urine collection, or estimated by the Cockcroft and Gault formula
• •* Calculated creatinine clearance must be \>= 30 ml/min using the Cockcroft-Gault formula
• •Negative pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
• •Female patients of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective (dual methods of) contraception throughout the study and for 6 months following the last dose of study drug; and male patients must use an effective barrier method of contraception throughout the study and for 3 months following the last dose of study drug if sexually active
• •Ability to complete questionnaire(s) by themselves or with assistance
• •Provide informed written consent =\< 28 days prior to registration
• •Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)