Inclusion Criteria:
* Diagnosis of triple-class exposed or refractory multiple myeloma. Diagnosis must be histologically confirmed. Patients with multiple myeloma with local amyloid deposition in the bone marrow are eligible.
* Received standard of care ciltacabtagene autoleucel (cilta-cel; Carvykti).
* High risk cytogenetics as defined by IMWG OR Presence of extramedullary disease documented prior to receiving CAR-T OR Patients with less than CR at Day 30 post CAR-T OR Patients with MRD-positive disease at Day 30 post CAR-T
* Able to monitor disease response by ClonoSEQ MRD testing.
* At least 18 years of age.
* ECOG performance status ≤ 2.
* Adequate bone marrow and organ function at Day 30 post CAR-T (+28 /-14 days) as defined below:
* Absolute neutrophil count ≥ 1.0 K/cumm
* Platelets ≥ 50 K/cumm
* Hemoglobin ≥ 8.5 g/dL without blood transfusion within 7 days before C1D1.
* Total bilirubin ≤ 1.5 x IULN; patients with Gilbert's syndrome must have a total bilirubin \< 3 x IULN.
* AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN
* Calculated creatinine clearance ≥ 15 mL/min by Cockcroft-Gault
* The effects of selinexor on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 90 days after completion of selinexor. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.
* Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
Exclusion Criteria:
* MM with active CNS involvement.
* Confirmed progressive disease by IMWG after CAR-T administration.
* Unresolved cytokine release syndrome (CRS) or CAR-T neurologic toxicity.
* Any unresolved non-hematologic grade ≥ 3 treatment-related toxicity from CAR-T.
* Administration or planned administration of any other concomitant chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy which would be considered a treatment of multiple myeloma from Day 28 post-CAR-T cell therapy through discontinuation from study treatment. Note: patients may be on corticosteroids if they are being given for disorders other than multiple myeloma (e.g., adrenal insufficiency, rheumatoid arthritis)
* Has received selinexor or another XPO1 inhibitor post-CART.
* Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
* Prior organ transplant requiring immunosuppressive therapy.
* Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial
* Currently receiving any other investigational agents.
* A history of allergic reactions attributed to compounds of similar chemical or biologic composition to selinexor or other agents used in the study.
* Active gastrointestinal dysfunction interfering with the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment.
* Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to CAR-T (patients on prophylactic antibiotics or with a controlled infection within 1 week prior to CAR-T may enroll); active, unstable cardiovascular function, as indicated by the presence of symptomatic ischemia, uncontrolled clinically significant conduction abnormalities (e.g. patients with ventricular or atrial tachycardia on anti-arrhythmics are excluded; patients with first degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block will not be excluded), congestive heart failure of NYHA class ≥ 3 or known left ventricular ejection fraction of \< 40%, or myocardial infraction within 3 months prior to CAR-T therapy.
* Major surgery within 28 days prior to CAR-T cell therapy.
* Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry.
* HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving effective anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible. HIV testing not required in the absence of known history of infection.
* Evidence of chronic hepatitis B virus (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible. HBV testing not required in the absence of known history of infection.
* History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing not required in the absence of known history of infection.
