嵌合抗原受体T细胞治疗复发/难治B细胞非霍奇金淋巴瘤患者的长期疗效

目的：评价嵌合抗原受体（CAR）T细胞治疗复发/难治B细胞非霍奇金淋巴瘤（B-NHL）的长期疗效。方法：收集2016年6月至2020年6月在浙江大学医学院附属第一医院骨髓移植中心应用CAR-T细胞治疗的27例复发/难治B-NHL患者的资料，随访日期截至2022年2月1日。运用Kaplan-Meier生存分析评估患者总存活率和无进展存活率，并统计相关不良反应。结果：27例患者中位随访时间为32（1，56）个月，CAR-T细胞治疗总反应率为85.2%（23/27），完全缓解率为63.0%（17/27），部分缓解率为22.2%（6/27）。患者3年总存活率为（50.0±10.1）%，无进展存活率为（44.4±9.6）%。CAR-T细胞治疗后获完全缓解患者的总存活率和无进展存活率均优于未获完全缓解患者总存活率分别为（66.9±12.7）%和（20.0±12.6）%，P＝0.01；无进展存活率分别为（64.7±11.6）%和（10.0±9.5）%，P<0.01]。CD19单靶点和CD19/CD22双靶点的CAR-T细胞治疗患者总存活率和无进展存活率差异无统计学意义（均P>0.05）。92.6%（25/27）的患者发生细胞因子释放综合征；88.9%（24/27）的患者治疗期间发生Ⅲ~Ⅳ级骨髓抑制；其他不良反应包括免疫效应细胞相关神经毒性综合征、乙型肝炎病毒激活以及肺部或胃肠道感染等。未观察到远期不良反应发生。结论：CAR-T细胞治疗是复发/难治B-NHL患者的有效治疗方案，不良反应可控。CAR-T细胞治疗后获得完全缓解及随访至1年时处于存活状态的患者可能有更好的长期存活率。

Long-term efficacy of CAR-T cell therapy for patients with relapsed/refractory B cell non-Hodgkin lymphoma

Objective: To evaluate the long-term efficacy of chimeric antigen receptor (CAR) T cell therapy in treatment of relapsed/refractory B cell non-Hodgkin lymphoma (B-NHL). Methods: Clinical data of 27 patients with relapsed/refractory B-NHL treated with CAR-T cell in Bone Marrow Transplantation Center, the First Affiliated Hospital of Zhejiang University School of Medicine from June 2016 to June 2020 were analyzed. Patients were followed up to February 1, 2022. The overall survival rate, progression free survival (PFS) rate were evaluated by Kaplan-Meier analysis, and the adverse reactions were recorded. Results: The median follow-up time of 27 patients was 32? (1, 56) months. The total response rate was 85.2% (23/27), the complete response rate was 63.0% (17/27), and the partial response rate was 22.2% (6/27). The 3-year overall survival rate was (50.0±10.1)%, and the PFS rate was (44.4±9.6)%. After CAR-T cell therapy, the overall survival and PFS of patients in the complete response group were significantly better than those in the non-complete response group overall survival rate: (66.9±12.7)% vs. (20.0±12.6)%, P=0.01; PFS rate: (64.7±11.6)% vs. (10.0±9.5)%, P<0.01]. There was no significant difference in overall survival rate and PFS rate between CD19 targeted and CD19/CD22 dual-targeted CAR-T cell therapy (bothP>0.05). Cytokine release syndrome developed in 92.6% (25/27) of patients, and 88.9% (24/27) of patients had grade Ⅲ–Ⅳ myelosuppression. Other adverse reactions include immune effector cell-associated neurotoxicity syndrome, hepatitis B virus activation, and lung or gastrointestinal infections. No long-term adverse reactions occurred.Conclusions: CAR-T cell therapy is effective for patients with relapsed/refractory B-NHL, and the adverse reactions are controllable. The patients who obtain complete response after CAR-T cell therapy or survive for one year after therapy may have better long-term survival.