CD19靶向的嵌合抗原受体T细胞治疗急性B淋巴细胞白血病伴髓外复发患者的疗效和安全性  

Efficacy and safety of CD19 CAR-T cell therapy for patients with B cell acute lymphoblastic leukemia involving extra-medullary relapse

作　　者：黄荦 张明明 魏国庆[1,2,3,4] 赵厚力[1,2,3,4] 胡永仙[1,2,3,4] 黄河 HUANG Luo;ZHANG Mingming;WEI Guoqing;ZHAO Houli;HU Yongxian;HUANG He(Bone Marrow Transplantation Center,the First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China;Liangzhu Laboratory,Zhejiang University Medical Center,Hangzhou 311121,China;Institute of Hematology,Zhejiang University,Hangzhou 310058,China;Zhejiang Provincial Laboratory for Stem Cell and Immunity Therapy,Hangzhou 310058,China)

机构地区：[1]浙江大学医学院附属第一医院骨髓移植中心,浙江杭州310003 [2]浙江大学医学中心良渚实验室,浙江杭州311121 [3]浙江大学血液学研究所,浙江杭州310058 [4]浙江省干细胞与细胞免疫治疗工程实验室,浙江杭州310058

出　　处：《浙江大学学报（医学版）》2022年第2期151-159,共9页Journal of Zhejiang University(Medical Sciences)

基　　金：国家自然科学基金(81730008,81870153)。

摘　　要：目的:评估CD19靶向的嵌合抗原受体(CAR)T细胞治疗急性B淋巴细胞白血病(B-ALL)伴髓外复发患者的疗效和安全性。方法:回顾性收集2016年1月至2021年10月在浙江大学医学院附属第一医院接受CD19靶向的CAR-T细胞治疗的15例B-ALL伴髓外复发患者的资料。采用Kaplan-Meier分析法评估患者的总存活率和无白血病存活率,观察不同部位的髓外病灶对CD19靶向的CAR-T细胞治疗的反应,并对CD19靶向的CAR-T细胞治疗期间细胞因子释放综合征(CRS)、血液学毒性、免疫效应细胞相关神经毒性综合征(ICANS)等不良反应进行统计分析。结果:15例患者中位随访时间为7(3~71)个月,最佳疗效为完全缓解11例(73.3%),中位完全缓解持续时间为6(2~27)个月;部分缓解3例(20.0%);疾病进展1例(6.7%)。CD19靶向的CAR-T细胞治疗总反应率达93.3%(14/15),随访终点总存活率为80.0%(12/15)。15例患者累计复发率和复发病死率分别为40.0%(6/15)和20.0%(3/15),目前9例(60.0%)患者无病生存。15例患者中,13例(86.7%)发生CRS,其中1~2级7例,3级6例;1例(6.7%)出现可逆性ICANS;15例(100.0%)出现B细胞发育不全;12例(80.0%)发生严重血液学不良反应;2例(13.3%)出现肝功能异常;1例(6.7%)出现肾功能异常;4例(26.7%)发生感染。上述不良反应均控制良好。结论:CD19靶向的CAR-T细胞治疗复发/难治B-ALL伴髓外复发患者疗效明确,不良反应控制良好。Objective:To evaluate the efficacy and safety of CD19 chimeric antigen receptor(CAR)T cell therapy for patients with B cell acute lymphoblastic leukemia(BALL)involving extramedullary relapse.Methods:Fifteen patients with B-ALL involving extramedullary relapse who received CD19 CAR-T cell therapy in the First Affiliated Hospital,Zhejiang University School of Medicine from January 2016 to October 2021 were enrolled in this study.The overall survival and leukemia-free survival of patients were analyzed using Kaplan-Meier curves,and the response of extramedullary lesions in different locations following the CD19 CAR-T cell therapy was observed.Cytokine release syndrome(CRS),hematological toxicity,and immune effector cell-associated neurotoxicity syndrome(ICANS)during CD19 CAR-T cell therapy were analyzed.Results:The median follow-up time was 7(3–71)months,and 11 cases(73.3%)achieved complete response,median duration of complete response was 6(2–27)months;3 cases(20.0%)achieved partial response;1 case(6.7%)got progressive disease.The overall response rate was 93.3%(14/15),and the overall survival rate was 80.0%(12/15)at the end of follow-up.The cumulative incidence of relapse was 40.0%(6/15)and relapse mortality rate was 20.0%(3/15).Until last follow-up date,9 cases(60.0%)were still in disease-free survival.Among the 15 patients,13 cases(86.7%)developed cytokine release syndrome(CRS)after cell infusion,including 7 cases with grade 1–2 CRS,6 cases with grade 3 CRS;1 case suffered from reversible ICANS;15 cases(100.0%)developed B cell dysplasia;12 cases(80.0%)developed severe hematologic adverse reactions;2 cases(13.3%)had abnormal liver function;1 case(6.7%)had abnormal renal function;4 cases(26.7%)developed infection.The adverse reactions mentioned above were well controlled.Conclusion:CD19 CAR-T cell therapy shows explicit efficacy and controllable adverse reactions for BALL patients with extramedullary relapse.

关 键 词：急性B淋巴细胞白血病 嵌合抗原受体T细胞 复发/难治 髓外复发 CD19 疗效 安全性 

分 类 号：R733[医药卫生—肿瘤]