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.

Inclusion Criteria: * Diagnosis of triple-class exposed or refractory multiple myeloma (MM). Diagnosis must be histologically confirmed. Patients with multiple myeloma with local amyloid deposition in the bone marrow are eligible. Only the following risk categories will be enrolled: * High risk myeloma, defined by the presence of at least one of the following features: * Deletion 17p and/or TP53 alteration: * Deletion of 17p with a cancer clonal fraction (CCF) ≥20%, assessed on CD138-positive/purified plasma cells, AND/OR * TP53 mutation identified using a validated next-generation sequencing (NGS)-based assay. * High-risk IgH translocation with chromosome 1 abnormality: * Presence of t(4;14), t(14;16), or t(14;20) in combination with either gain/amplification of 1q (1q+) and/or deletion of 1p32. * Chromosome 1p32 deletion patterns: * Monoallelic deletion of 1p32 occurring with gain/amplification of 1q, OR * Biallelic deletion of 1p32. * Elevated β2-microglobulin without renal dysfunction: * Serum β2-microglobulin ≥5.5 mg/L in the setting of normal renal function, defined as serum creatinine \