Selinexor combined with R-GDP as salvage therapy in relapsed/refractory diffuse large B-cell lymphoma

Relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) remains a therapeutic challenge with poor prognosis. Selinexor, a selective inhibitor of nuclear export (XPO1), has shown activity in this setting. We retrospectively evaluated the efficacy and safety of selinexor combined with R-GDP (rituximab, gemcitabine, dexamethasone, and cisplatin) as second-line therapy in 22 patients with R/R DLBCL treated at Fudan University Shanghai Cancer Center between January 2023 and August 2023. Patients were scheduled to receive 3 cycles of selinexor plus R-GDP, and subsequently followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT), anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy, or alternative regimens, as appropriate. At a median follow-up of 25.5 months, the selinexor plus R-GDP regimen yielded an overall response rate of 52.4% in patients with R/R DLBCL. The median overall survival (OS) was 26.9 months (95% CI, 12.1-not reached), with 1- and 2-year OS rates of 67.6% and 52.3%. The median progression-free survival (PFS) was 7.7 months (95% CI, 2.27-not reached). Survival outcomes were significantly influenced by subsequent therapy: patients bridged to ASCT or CAR-T therapy had significantly longer OS (P=0.0217) and PFS (P=0.0029) than those receiving other treatments. The median OS was not reached in the ASCT group, 26.9 months (95% CI, 15.9-not reached) in the CAR-T group, and 11.2 months (95% CI, 10.2-not reached) in patients receiving other therapies. The median PFS was not reached for ASCT or CAR-T group, compared with 2.2 months (95% CI, 2.1-not reached) in patients receiving other therapies. Additionally, patients with relapsed disease exhibited a significantly longer median PFS than those with primary refractory disease (not reached vs 2.82 months, [95% CI, 2.17-not reached]; P=0.0072). No significant difference in OS was observed between these two groups (P=0.2323). Common adverse events included thrombocytopenia (100%), fatigue (59%), neutropenia (45%), anemia (45%), and pneumonia (23%), while were manageable through supportive care or temporary dose interruption. In this real-world analysis, selinexor combined with R-GDP demonstrated modest efficacy in R/R DLBCL, while highlighting the importance of optimizing subsequent sequencing with ASCT or CAR-T therapy.