lisocabtagene maraleucel 用于复发/难治性 PMBCL 中 PD-1 阻断后的安全性与有效性

Primary mediastinal B-cell lymphoma (PMBCL) is a distinct subtype of large B-cell lymphoma characterized by 9p24. 1 copy-number alterations and PD-1-mediated immune evasion. This profile confers high sensitivity to PD-1 inhibitors such as pembrolizumab. CD19-directed chimeric antigen receptor (CAR) T-cell therapies have shown benefit in relapsed or refractory (R/R) PMBCL, but their optimal role remains undefined.

We retrospectively analyzed 31 patients with R/R B-cell lymphoma treated with lisocabtagene maraleucel (liso-cel), including four with PMBCL who received pembrolizumab prior to CAR-T. All four achieved remission before infusion, and three maintained durable complete responses ( 30 months).

Toxicities were comparable to those in patients not treated with pembrolizumab, although one pembrolizumab-treated patient experienced fatal neurotoxicity. Favorable hematologic recovery and preserved T-cell counts at leukapheresis suggest that preceding PD-1 blockade did not compromise CAR-T manufacturing and may have enhanced T-cell fitness.

These findings suggest that sequential PD-1 blockade followed by liso-cel is clinically feasible and may improve outcomes by leveraging the immune vulnerability of PMBCL. While prior studies have focused on axicabtagene ciloleucel, this report provides the first real-world data supporting the feasibility and potential benefit of this approach with liso-cel. Prospective studies are needed to confirm efficacy, safety, and optimal sequencing.