人源化靶向CD19 CAR-T细胞治疗复发/难治急性B淋巴细胞白血病的有效性及安全性  

Safety and efficacy of humanized CD19-targeted CAR-T cells in patients with relapsed/refractory acute B cell lymphoblastic leukemia

作　　者：宋凤美 胡永仙[1] 张明明 吴文俊[1] 徐惠君 张鸿声[2] 黄河[1] 魏国庆[1] Song Fengmei;Hu Yongxian;Zhang Mingming;Wu Wenjun;Xu Huijun;Zhang Hongsheng;Huang He;Wei Guoqing(Bone Marrow Transplantation Center,Institute of Hematology,The First Affiliated Hospital,College of Medicine,Zhejiang University,Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy,Zhejiang Laboratory for Systems&Precision Medicine,Zhejiang University Medical Center,Hangzhou 311100,China;Clinical Transformation Center,Shanghai Pulmonary Hospital,Tongji University School of Medicine,Shanghai 200438,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,浙江大学良渚实验室,浙江大学血液学研究所,浙江省干细胞与细胞免疫治疗工程实验室,浙江311100 [2]同济大学医学院附属肺科医院临床转化中心,上海200438

出　　处：《中华血液学杂志》2022年第8期651-656,共6页Chinese Journal of Hematology

基　　金：国家自然科学基金重点项目(81730008、82130003);国家自然科学基金面上项目(81870153);浙江省重点研发计划(2019C03016、2018C03016-2)。

摘　　要：目的观察人源化靶向CD19嵌合抗原受体T细胞(CAR-T)治疗复发/难治急性B淋巴细胞白血病(R/R B-ALL)患者的有效性及安全性。方法分析2020年2月至2021年7月于浙江大学医学院附属第一医院接受人源化靶向CD19 CAR-T细胞治疗的41例R/R B-ALL患者的有效性和安全性。结果中位第15(9~47)天,41例患者的完全缓解率为95.1%(39/41),其中38例患者骨髓经流式细胞术检测微小残留病灶阴性。39例完全缓解的患者中17例未接受进一步治疗,70.6%(12/17)的患者在随访结束时仍处于缓解状态,输注最早的两例患者无进展生存期达12.6个月;另外17例患者缓解后行巩固性造血干细胞移植(10例)或CD22 CAR-T细胞序贯治疗(7例),76.5%(13/17)的患者在随访结束时仍处于缓解状态;其余5例患者未接受巩固性治疗,在CAR-T细胞治疗后中位第72(55~115)天复发。1年总生存率为73.6%(95%CI 55.2%~92.3%),1年无进展生存率为56.2%(95%CI 38.1%~75.2%)。所有患者均发生了细胞因子释放综合征,63.4%(26/41)为1~2级。3例患者发生免疫效应细胞相关神经毒性综合征。结论人源化靶向CD19 CAR-T细胞能有效诱导R/R B-ALL患者获得完全缓解,且不良反应可耐受。Objective This study aimed to evaluate the safety and efficacy of humanized CD19-targeted chimeric antigen receptor T-cell(CAR-T)in patients with relapsed/refractory acute B cell lymphoblastic leukemia(R/R B-ALL).Methods The clinical data of 41 patients with R/R B-ALL treated with humanized CD19-targeted CAR-T cells in the First Affiliated Hospital of Zhejiang University School of Medicine from February 2020 to July 2021 were analyzed.Results Cytokine release syndrome occurred in all patients,and 63.4%(26/41)were grades 1-2.Immune effector cell-associated neurotoxicity syndrome developed in three patients.On median day 15(9-47),the complete remission rate was 95.1%(39/41),of which 38 patients tested negative for bone marrow minimal residual disease detected by flow cytometry.Among the 39 patients with complete remission,17 patients did not receive further treatment,and 70.6%(12/17)remained in remission at the end of follow-up,with a progression-free survival of 11.6 months of the two patients with the earliest infusion.Another 17 patients underwent consolidation allogeneic hematopoietic stem cell transplantation(10 cases)or CD22 CAR-T cell sequential therapy(seven cases)after remission,and 76.5%(13/17)of the patients were still in remission at the end of follow-up.The remaining five patients who did not receive consolidation therapy relapsed at a median of 72(55-115)days after CAR-T cell therapy.Conclusion In patients with R/R B-ALL,the humanized CD19-targeted CAR-T cells had a high response and manageable toxicity.

关 键 词：嵌合抗原受体 人源化 急性淋巴细胞白血病 难治 复发 

分 类 号：R733.71[医药卫生—肿瘤]