HCMT/MM2401: Ph2 Study of Selinexor + Bispecific Antibody for RRMM

The primary objectives of this study are to determine the safety of single agent Selinexor given with commercial bispecific antibody therapy in patients with Relapsed/Refractory Multiple Myeloma (RRMM) and to determine the MRD negativity rate at 10-5 at 12 months post bispecific antibody therapy. The investigators will enroll 27 patients with RRMM who are receiving commercial bispecific antibody therapy. Patients will be on treatment for 12 months or until disease progression, and will be followed for 24 months. Study assessments include completing a drug diary, having a safety check in call, and have history, clinical assessments, and labs taken. Twenty-seven patients will provide 80% power in a one-sample chi square test for a proportion assuming that the rate of negative MRD at 10-5 at 12 months post bispecific antibody therapy is 25% in historical control and 50% in the SEL+bispecific antibody experimental treatment group, under a one-sided 5% significance level.

Inclusion Criteria: 1. Age ≥ 18 years old at the time of informed consent. 2. Willing and able to provide written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure. 3. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 4. A diagnosis of symptomatic multiple myeloma, with relapsed or refractory disease. Patients must have received at least 4 prior lines of therapy. Prior lines of therapy must include a proteasome inhibitor, an immunomodulatory agent, and an CD38 monoclonal antibody, and may include treatment with BCMA antibody conjugates or BCMA directed chimeric antigen receptor (CAR) T cell therapy. 5. All patients must meet criteria for and will receive teclistamab, elranatamab or talquetamab, as per approved label dosing. 6. Patients who have had CRS/ICANS from bispecific antibody must have complete resolution of CRS/ICANS before initiation of SEL 7. Measurable disease as defined by at least one of the following: * Serum monoclonal (M) protein ≥1.0 g/dl by protein electrophoresis * \>200 mg of M protein in the urine on 24 hour electrophoresis * Serum immunoglobulin free light chain ≥10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio * Measurable plasmacytoma 8. Adequate hepatic function measured on labs collected within 28 days of C1D1: * Total bilirubin \