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 <1.5 × upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of <3 × ULN), and
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to <2.5 × ULN.
9. Adequate renal function measured on labs collected within 28 days of C1D1. Adequacy will be determined by creatinine clearance with values of ≥ 15 mL/min meeting inclusion criteria. Creatinine Clearance will be calculated using the Cockcroft and Gault formula [(140 - Age) x Mass (kg)/ (72 x creatinine mg/dL); multiply by 0.85 if female] (Cockcroft 1976).
10. Adequate hematopoietic function measured on labs collected within 7 days of C1D1:
* Absolute neutrophil count ≥1500/mm3
* Hemoglobin ≥8.5 g/dL
* Platelet count ≥100,000/mm3 (patients for whom <50% of bone marrow nucleated cells are plasma cells) or ≥50,000/mm3 (patients for whom ≥50% of bone marrow nucleated cells are plasma cells)
* Note 1: Patients receiving hematopoietic growth factor support, including erythropoietin, darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and platelet stimulators (e.g., eltrombopag, romiplostim, interleukin-11) are eligible.
* Note 2: Patients must have at least a 1-week interval from the last platelet transfusion prior to the Screening platelet assessment. However, patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study.
11. Patients who are able to become pregnant must have a negative serum pregnancy test at screening.
12. All patients who could become pregnant or could father a child must use highly effective methods of contraception throughout the study and for 5 months following the last dose of study treatment. Highly effective methods of contraception are listed in Section 9.3.1.
13. Female patients must agree not to donate egg during the study treatment period and/or up to 90 days after the last dose of Selinexor. Male patients must agree not to donate sperm during the study treatment period and/or up to 90 days after the last dose of Selinexor.