Selinexor-based regimens in triple-class exposed or refractory multiple myeloma: A real-world analysis of efficacy and safety in 18 patients

Abstract Background: Patients with triple-class exposed (TCE) or triple-class refractory (TCR) multiple myeloma (MM) have limited therapeutic options and a dismal prognosis. Selinexor, a selective inhibitor of nuclear export (SINE), targets exportin-1 (XPO1) to restore tumor suppressor function. This study evaluates selinexor-based regimens in this population. Methods: In this single-center retrospective study, consecutive patients with TCE or TCR MM treated with selinexor-based combination regimens between October 1, 2023, and March 31, 2025, were enrolled. Efficacy, assessed per International Myeloma Working Group (IMWG) criteria, included primary endpoints of overall response rate (ORR) and progression-free survival (PFS). Results: Eighteen patients with relapsed/refractory MM were treated over 18 months, comprising 6 TCE and 12 TCR patients. Median age was 61 years (40–73); 12/18 (66.7%) were male. Pre-treatment baseline characteristics revealed high-risk disease features: extramedullary plasmacytomas (3/18, 16.7%), secondary plasma cell leukemia (3/18, 16.7%), and renal insufficiency (3/18, 16.7%). The median number of prior lines of therapy was 5 (2–9). Treatment regimens included selinexor (40–60 mg/week) combined with the KPD regimen (carfilzomib, pomalidomide, dexamethasone) in 6/18 (33.3%) patients; other combinations comprised cytotoxic drugs, aponermin, daratumumab, and venetoclax. Patients received a median of 5.5 treatment cycles (range: 3–11). The overall response rate (ORR) was 12/18 (66.7%), with responses as follows: complete response (CR) in 5/18 (27.8%), very good partial response (VGPR) in 3/18 (16.7%), partial response (PR) in 4/18 (22.2%), minimal response (MR) in 4/18 (22.2%), stable disease (SD) in 1/18 (5.6%), and progressive disease (PD) in 1/18 (5.6%). With a median follow-up of 9.7 months (95% CI: 8.6–12.5), median progression-free survival (PFS) was 10.9 months (95% CI: 2.7–19.1). Grade ≥3 hematologic adverse events (AEs) included neutropenia (13/18, 72.2%), anemia (6/18, 33.3%), and thrombocytopenia (5/18, 27.8%). The most common non-hematologic AEs were nausea (11/18, 61.1%) and fatigue (8/18, 44.4%). Treatment discontinuation due to AEs occurred in 3/18 (16.7%) of patients. There were no treatment-related deaths. Conclusion: Selinexor-based regimens demonstrate clinically meaningful efficacy (ORR 66.7%, median PFS 10.9 months) and a manageable safety profile in heavily pretreated TCE/TCR RRMM patients. These findings support its use as a viable salvage therapy. Further validation through larger prospective trials is warranted to confirm these results.