靶向CD19嵌合抗原受体T细胞(C-CAR011)治疗复发难治B细胞非霍奇金淋巴瘤  

Anti-CD19 CART( C-CAR011) Therapy for Relapsed or Refractory B Cell Non Hodgkin Lymphoma

作　　者：龚帅格 王甫珏 王烁婷 郑沁[2] 帅晓[1] 马洪兵[1] 张丽[1] 陈心传[1] 吴俣[1] 贾永前[1] GONG Shuai-Ge;WANG Fu-Jue;WANG Shuo-Ting;ZHENG Qin;SHUAI Xiao;MA Hong-Bing;ZHANG Li;CHEN Xin-Chuan;WU Yu;JIA Yong-Qian(Department of Hematology,West China Hospital of Sichuan University,Chengdu 610041,Sichuan Province,China;Department of Laboratory Medicine,West China Hospital of Sichuan University,Chengdu 610041,Sichuan Province,China)

机构地区：[1]四川大学华西医院血液科,四川成都610041 [2]四川大学华西医院实验医学科,四川成都610041

出　　处：《中国实验血液学杂志》2021年第4期1141-1147,共7页Journal of Experimental Hematology

基　　金：西比曼生物科技(上海)有限公司资助。

摘　　要：目的:评价靶向CD19嵌合抗原受体T细胞注射液C-CAR011治疗复发或难治性B细胞非霍奇金淋巴瘤(R/R B-NHL)患者的安全性和有效性。方法:入选的R/R B-NHL患者,予淋巴细胞清除术及CD19 CART输注治疗(C-CAR011 5.0×10^(6)/kg)后,随访至CD19 CART治疗后1年。主要研究终点是安全性;次要研究终点包括第4周、12周、6个月与12个月患者的总缓解率(ORR)、无疾病进展(PFS)、缓解持续时间(DOR)的情况,以及第12周、第6和12个月的总生存期(OS)。结果:6例R/R B-NHL受试者接受C-CAR011治疗及随访,中位年龄为46.5(37-62)岁,男女比例为1∶1,5例患者为弥漫大B细胞淋巴瘤(DLBCL),1例患者为滤泡淋巴瘤(FL)。治疗后主要不良反应为血液学毒性(发生率100%,均为3-4级),细胞因子释放综合征(CRS)(发生率66.7%,1-3级),神经毒性(发生率16.7%,3级),均可控且可逆。在4、12周和6、12个月获得OR的患者分别有3例、3例、1例和1例,有3例患者最佳疗效为完全缓解(CR),其中1例在1年评估时仍保持CR。中位PFS为178(91-> 365) d。曾经获得缓解的3例患者的DOR分别为150、154 d和12个月以上。患者的OS率在第12周、6个月和12个月时分别为100%、100%和83.3%,而中位OS未达到。结论:C-CAR011可安全的用于R/R B-NHL,且可在部分患者中获得长期持续疗效(研究注册号:NCT03483688)。Objective: To evaluate the safety and efficacy of C-CAR011 in the treatment of relapsed or refractory Bcell non-Hodgkin lymphoma( R/R B-NHL) patients. Methods: B-NHL patients treated with C-CAR011 infusion following lympho-depletion were enrolled. All the patients were followed up for 1 year after C-CAR011 treatment( 5. 0 ×10^(6)/kg). The primary endpoint of this research was safety;and the secondary endpoints included objective response rate( ORR),progression-free survival( PFS),duration of overall response( DOR),overall survival( OS) at Week 4,12 and Month 6 and 12. Results: The ratio of the male and female of 6 patients was 1∶ 1,and the patients were treated with C-CAR011 at a dose of 5. 0 × 10^(6)/kg. The median age was 46. 5 years old( 37-62 years);5 patients were diagnosed as diffuse large b-cell lymphoma( DLBCL) and 1 patient was diagnosed as follicular lymphoma( FL). The most common adverse events( AEs) were hematological toxicities( 100%,Grade 3-4),cytokine release syndrome( CRS)( 66. 7%,Grade 1-3),neurotoxicity( 16. 7%,Grade 3). All these AEs were reversible and could be conversed. The ORR at Week 4,12 and Month 6,12 were 50%( 3/6),50%( 3/6),16. 7%( 1/6) and 16. 7%( 1/6),respectively.Three patients( 50%) achieved complete response( CR) and one of them stayed evaluated as CR until Month 12. The median PFS was 178 days( 91-> 365 days). For 3 patients with response,the DOR were 150 days,154 days and> 12 months,respectively. The OS rates of the patients at Week 12,Month 6,12 were 100%,100%,83. 3%,respectively,while the median OS was not reached. Conclusion: C-CAR011 is a safe treatment option for R/R B-NHL;some patients could achieve long-term sustained responses after C-CAR011 infusion( ClinicalTiral. gov number,NCT03483688).

关 键 词：CD19 CART 非霍奇金淋巴瘤 安全性 有效性 

分 类 号：R733.71[医药卫生—肿瘤]