复发/难治性大B细胞淋巴瘤CAR-T治疗失败后的挽救策略探索OA

Objective To evaluate the efficacy of different salvage regimens after chimeric antigen receptor T cell(CAR-T)therapy failure and explore relevant prognostic factors,so as to provide reference for clinical decision-making.Methods A retrospective analysis was conducted of 29 patients with relapsed/refractory large B-cell lymphoma(R/R LBCL)who received salvage treatment after progression/recurrence following CAR-T therapy at Beijing Tongren Hospital from April 2022 to December 2024.Salvage regimens were categorized into 6 groups:bispecific antibodies-based regimens,secondary CAR T-cell infusion,radiotherapy,Polatuzumab vedotin-based(Pola-based)regimens,immune checkpoint inhibitors,and other targeted/chemotherapy drugs.The primary endpoint was overall survival(OS),defined as the time from the first CAR-T reinfusion to death from any cause or the last follow-up.Secondary endpoints included:objective response rate(ORR),complete response(CR),partial response(PR),duration of response(DOR)for different salvage regimens.Univariable Cox re-gression analysis was performed to explore independent risk factors affecting OS after CAR-T therapy failure.Results After a median follow-up of 7.0 months,the median OS of the 29 enrolled patients rate was 7.0 months(range:1.0-15.0 months).Among the total 58 salvage treatment events,the overall ORR was 41.4%(24/58),and the CR rate was 12.1%(7/58).The Polatuzumab vedotin-based therapy demon-strated the highest ORR(66.7%);and the secondary CAR-T regimen demonstrated the highest CR rate(30.0%),with a CR rate of 60.0%for target-switching CAR-T.Fever was the most common adverse event of salvage therapy.Univariable analysis revealed that patients with late relapse had better OS than those with early relapse(HR=0.44;95%CI:0.21-0.95;P=0.038).Conclusions The prognosis after CAR-T therapy failure is poor,and patients with late relapse have better OS.After CAR-T failure,switching to a different CAR-T target for salvage therapy may yield higher CR rates.The pola-based regimen shows a high ORR,but achieving durable clinical benefit remains a challenge.