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. 2025 Feb 16;14(4):1316.
doi: 10.3390/jcm14041316.

Impact of Prior Selinexor Exposure on Outcomes of Chimeric Antigen Receptor T-Cell Therapy for Relapsed/Refractory Multiple Myeloma: An Exploratory Analysis

Bruno Almeida Costa  1 , Danai Dima  2 , Tomer Mark  3 , Norah Layla Sadek  1 , Stephen Ijioma  3 , David Ray  3 , Utkarsh Goel  4 , George Dranitsaris  5 , Tianxiang Sheng  1 , Erin Moshier  1 , Tarek H Mouhieddine  1 , Jack Khouri  4 , Adriana Rossi  1
Affiliations

Impact of Prior Selinexor Exposure on Outcomes of Chimeric Antigen Receptor T-Cell Therapy for Relapsed/Refractory Multiple Myeloma: An Exploratory Analysis

Bruno Almeida Costa et al. J Clin Med. .

Abstract

Background/Objectives: Chimeric antigen receptor T-cell therapy (CAR-T) has become a key treatment option for relapsed/refractory multiple myeloma (RRMM), but factors impairing T-cell fitness may diminish efficacy. Our exploratory analysis aimed to evaluate the impact of prior treatment with a selinexor-containing regimen on CAR-T outcomes for RRMM patients. Methods: Data for this retrospective cohort study were sourced from electronic medical records at two US academic centers. Kaplan-Meier estimates assessed duration of response (DOR), progression-free survival (PFS), and overall survival (OS), reported as medians with interquartile ranges (IQRs). Cox proportional hazards regression analyzed factors potentially associated with PFS and OS, reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Among 45 patients exposed to selinexor before undergoing BCMA-directed CAR-T, median therapy line numbers for selinexor use and CAR-T were 7 and 9, respectively, with 24.4% receiving selinexor as part of bridging. At median follow-up of 68 months, median PFS and OS post CAR-T were 8.0 (IQR 3.1-39.5) and 35.9 (IQR 14.2-NR) months, respectively. Overall response rate to CAR-T was 89%, with a median DOR of 8.1 months (IQR 2.9-39.0). In our multivariable model, patients who received a selinexor-based regimen in the line of therapy preceding CAR-T showed a trend toward reduced risk of death (HR = 0.08; 95% CI 0.02-0.46) and/or disease progression (HR = 0.40; 95% CI 0.14-1.09). Conclusions: Prior selinexor exposure does not appear to compromise CAR-T outcomes in heavily pretreated RRMM, suggesting potential T-cell sparing. Our findings warrant larger, prospective studies to determine whether preemptive selinexor treatment can optimize CAR-T efficacy.

Keywords: CAR-T; T-cell exhaustion; T-cell fitness; XPO1; multiple myeloma; selinexor.

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Conflict of interest statement

T.M., D.R. and S.I. are employees of Karyopharm Therapeutics Inc. G.D. has acted as a consultant to the sponsor. J.K. has received honoraria from GPCR therapeutics and Janssen, J.K. has received consulting fees from Janssen and Prothena. A.R. has received consulting fees from Johnson & Johnson, Brystol Myers Squibb, Adaptive, Sanofi, and Karyopharm Therapeutics. U.G., B.A.C., N.S. and D.D. have no conflicts of interest.

Figures

Figure 1
Figure 1
Progression-free survival if selinexor was used in the immediate prior line of therapy before CAR-T therapy.
Figure 2
Figure 2
Overall survival if selinexor was used in the immediate prior line of therapy before CAR-T therapy.
See this image and copyright information in PMC

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