塞利尼索联合 R-GDP 作为复发/难治性弥漫大 B 细胞淋巴瘤挽救治疗

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.