Selinexor Maintenance Post CAR-T Cell Therapy for Multiple Myeloma
The outcomes in patients with relapsed multiple myeloma refractory to triple-therapy (anti-CD38, immunomodulatory drugs (IMiD) and proteasome inhibitors (PI)) remain poor. These patients are eligible for chimeric antigen receptor T-cells (CAR-T), which rely on redirecting autologous T-cells to clear myeloma cells by targeting B-cell maturation antigen (BCMA). BCMA CAR-T therapy is not curative, and unlike autologous stem cell transplant, there is currently no standard for maintenance therapy post CAR-T which could potentially increase MRD rates and extend progression-free survival. Selinexor is an exportin (XPO1) inhibitor with direct anti-tumor effect used often as an adjunct with other agents as bridging therapy prior to CAR-T. As selinexor does not affect T-cell yields or fitness, T-cell collection on selinexor for CAR-T manufacturing is safe. The aim of this study is to evaluate the safety and toxicity of selinexor in triple-exposed or refractory multiple myeloma patients with high-risk features (adverse risk cytogenetics, less than complete response (CR) post CAR-T, or extramedullary disease) following BCMA CAR-T therapy. The investigators hypothesize that selinexor as maintenance therapy following CAR-T has the potential to act synergistically with CAR-T cells leading to more durable responses.
• 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.