73例嵌合抗原受体T细胞治疗产品可疑且非预期严重不良反应

doi:10.19803/j.1672-8629.2020.09.12

中国药物警戒 ›› 2020, Vol. 17 ›› Issue (9): 600-606.
DOI: 10.19803/j.1672-8629.2020.09.12

73例嵌合抗原受体T细胞治疗产品可疑且非预期严重不良反应

李艳蓉, 杨策, 刘文东, 马润镒, 姚珠星, 胡洋平, 刘敏, 裴小静, 王海学^*

国家药品监督管理局药品审评中心,北京 100022

收稿日期:2020-08-17 修回日期:2020-08-17 出版日期:2020-09-15 发布日期:2020-08-17
通讯作者: ^*王海学,男,博士,主任药师,药理毒理。E-mail:wanghx@cde.org.cn
作者简介:李艳蓉,女,博士,主治医师,临床试验监管。

Seventy-three Cases of Suspected Unexpected Serious Adverse Reactions Reports with Chimeric Antigen Receptor T-cell Therapy Products

LI Yanrong, YANG Ce, LIU Wendong, MA Runyi, YAO Zhuxing, HU Yangping, LIU Min, PEI Xiaojing, WANG Haixue^*

Center for Drug Evaluation, NMPA, Beijing 100022, China

Received:2020-08-17 Revised:2020-08-17 Online:2020-09-15 Published:2020-08-17

摘要/Abstract

摘要： 目的对来自临床试验嵌合抗原受体T细胞(CAR-T细胞)治疗产品的可疑且非预期严重不良反应(SUSAR)报告进行分析和总结。方法对2018年5月1日至2019年8月31日国家药品监督管理局药品审评中心(CDE)接收的CAR-T细胞治疗产品的SUSAR个例安全性报告进行回顾性分析。结果 CDE共接收73例CAR-T细胞治疗产品的SUSAR报告。从2018年8月接收到第1份报告开始,SUSAR报告递交的数量呈逐渐增加趋势。受试者中男女比例为54.1%和45.9%。60~69岁的受试者最多,为39.7%,来自国内的SUSAR报告6份,为8.2%,Ⅰ/Ⅱ期临床试验的SUSAR报告最多,为43.8%,≥3级不良反应构成比为69.6%。不良反应累及系统-器官主要为神经系统疾病和全身性疾病及给药部位反应等。细胞因子释放综合征和CAR-T相关的脑病综合征报告率为39.6%和23.3%。共有13例受试者死亡,死亡原因主要为肿瘤进展和重度感染。结论申办者应建立健全药物警戒制度和体系,按时限递交SUSAR报告,提高报告质量。监管部门也会对SUSAR报告进行监测和评价,以保障临床试验期间受试者的用药安全。

关键词: 嵌合抗原受体T细胞, 可疑且非预期严重不良反应, 药物警戒, 安全性

Abstract: Objective To assess the suspected unexpected serious adverse reaction (SUSAR) reports of chimeric antigen receptor T (CAR-T) cells therapy products under clinical trials received by the Center for Drug Evaluation and National Medical Products Administration. Methods The SUSAR individual case safety reports of CAR-T therapy products received between May 1, 2018 and August 31, 2019 were retrieved from the pharmacovigilance database and analyzed retrospectively. Results A total of 73 SUSAR reports of CAR-T cells therapy products were received. An overall increase in the number of SUSAR reports was observed. The percentage of males and females was 54.1% and 45.9%, respectively. Most of the reported SUSARs involved subjects aged 60 to 69 (39.7%). The number of SUSAR reports from China was six (8.2%). The percentage of phase I/II clinical trials was the highest (43.8%). The percentage of grade 3 or above was 69.6%. Nervous system disorders, general disorders and administration site conditions were among the most commonly reported system organ class (SOC). The percentage of CRS and CRES was 39.6% and 23.3% respectively. Thirteen cases of death were identified in the pharmacovigilance database. Progression of cancer and severe infections were the main causes of death. Conclusion Sponsors should establish pharmacovigilance systems, submit reports of SUSARs as scheduled, and improve the quality of reports. In addition, regulators are expected to monitor and evaluate SUSARs to ensure the safety of subjects during clinical trials.

Key words: chimeric antigen receptor T cell, suspected unexpected serious adverse reaction, pharmacovigilance, safety

中图分类号:

R994.11

李艳蓉, 杨策, 刘文东, 马润镒, 姚珠星, 胡洋平, 刘敏, 裴小静, 王海学. 73例嵌合抗原受体T细胞治疗产品可疑且非预期严重不良反应[J]. 中国药物警戒, 2020, 17(9): 600-606.

LI Yanrong, YANG Ce, LIU Wendong, MA Runyi, YAO Zhuxing, HU Yangping, LIU Min, PEI Xiaojing, WANG Haixue. Seventy-three Cases of Suspected Unexpected Serious Adverse Reactions Reports with Chimeric Antigen Receptor T-cell Therapy Products[J]. Chinese Journal of Pharmacovigilance, 2020, 17(9): 600-606.

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73例嵌合抗原受体T细胞治疗产品可疑且非预期严重不良反应

Seventy-three Cases of Suspected Unexpected Serious Adverse Reactions Reports with Chimeric Antigen Receptor T-cell Therapy Products

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