P-386: Effect of Prior Selinexor Exposure on Clinical Outcomes of Chimeric Antigen Receptor T-cell (CAR-T) Therapy for Relapsed/Refractory Multiple Myeloma (RRMM): A Real-World Descriptive Analysis

Introduction: Chimeric Antigen Receptor T-cell (CAR-T) therapy is an active new T-cell based treatment in RRMM that is resource intensive and can be logistically difficult. Alkylating agents and proteasome inhibitors, amongst other patient and disease-related factors, have been shown to decrease T-cell fitness and may affect the efficacy of T-cell-redirecting therapies. In this real-world study, we investigate whether prior treatment with a selinexor-containing regimen impacts clinical outcomes in patients with RRMM after CAR-T therapy.

Methods: This retrospective cohort study analyzed medical records of 45 patients who received a selinexor-containing regimen prior to B-cell maturation antigen-directed CAR-T therapy at two academic cancer centers in the US. Baseline data collection encompassed patient demographics, disease characteristics, and prior treatments. From the CAR-T infusion date until last follow-up (12/01/2023), data were collected on hematological parameters, adverse events, response rates, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). PFS and OS curves following CAR-T therapy were generated using the Kaplan-Meier method.

Results: The median age at CAR-T infusion was 64 years, with 80% of patients classified as International Staging System Stage I or II. The CAR-T products given included idecabtagene vicleucel (60%), ciltacabtagene autoleucel (35.6%), and BMS-986354 (4.4%). Approximately 68.9% of patients received a bridging regimen following apheresis. Selinexor and CAR-T were frequently administered at the median 7th and 9th lines of treatment, respectively. The most common selinexor-based regimens were selinexor+bortezomib+dexamethasone (28.9%) and selinexor+carfilzomib+dexamethasone (20%), with 75.6% of patients starting selinexor at a dose ≤ 80 mg and 24.4% at dose ≥ 100mg. The median duration of selinexor therapy was 2.7 months. Only 24.4% of patients received selinexor as part of bridging therapy. Median DOR to CAR-T therapy was 8.1 months (IQR: 2.9 to 39), with 88.9% of patients achieving at least a partial response. The median DOR for ciltacabtagene autoleucel and idecabtagene vicleucel were 9.9 months (IQR: 10.1 to 13.8) and 7.2 months (IQR: 2.6 to 18.9), respectively. At a median follow-up of 68 months the median PFS and OS post CAR-T administration were 8.0 and 35.9 months, respectively. While 75.6% of patients experienced cytokine release syndrome (all grade I or II), 17.8% experienced immune effector cell-associated neurotoxicity syndrome (ICANS), with grade 3 ICANS in only 2 patients.

Conclusions: In this retrospective analysis, CAR-T clinical outcomes in heavily pretreated RRMM were unaffected by prior selinexor treatment. Further studies are warranted to examine the effect of specific selinexor combinations on clinical outcomes, including promoting an anti-tumor immune microenvironment, particularly pre-, post- and in-between CAR-T and other T-cell engaging regimens.