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中国癌症防治杂志

中国癌症防治杂志 ›› 2024, Vol. 16 ›› Issue (5): 554-561.doi: 10.3969/j.issn.1674-5671.2024.05.07

• CAR-T细胞治疗专栏 • 上一篇    下一篇

CD19 CAR⁃T细胞治疗的安全性:基于FAERS数据库的不良反应事件信号挖掘与分析

  

  1. 天津医科大学肿瘤医院淋巴瘤内科/国家恶性肿瘤临床医学研究中心/药物成药性评价与系统转化全国重点实验室/天津市恶性肿瘤临床医学研究中心；济南市第四人民医院心血管内科
  • 出版日期:2024-10-25 发布日期:2024-11-06

Safety of CD19 CAR-T therapy: Signal mining and analysis of adverse events based on FAERS database

  • Online:2024-10-25 Published:2024-11-06

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摘要： 目的 分析目前已上市的CD19 嵌合抗原受体T（chimeric antigen receptor T，CAR⁃T）细胞药物在治疗中出现的不良反应事件（adverse effect，AE），为临床用药提供依据。方法 使用美国食品药品监督管理局不良事件报告系统（FDA adverse event reporting system，FAERS）数据库，经过数据检索、筛选、去重、整理和分析等处理后，获取4种已上市的CD19 CAR⁃T药物阿基仑赛（Axicabtagene ciloleucel，Axi⁃cel）、替沙仑赛（Tisagenleucel，Tisa⁃cel）、布瑞基奥仑赛（Brexucabtagene autoleucel，Brexu⁃cel）和瑞基奥仑赛（Lisocabtagene maraleucel，Liso⁃cel）2017年第1季度至2023年第4季度的基线资料和AE结果。采用报告比值比（reporting odds ratio，ROR）法和比例报告比值比（proportional ADR reporting ratio，PRR）法分析和比较其AE。结果 本研究利用FAERS数据库，共得到 4种已上市的CD19 CAR⁃T药物的AE报告5 335份。4种CD19 CAR⁃T药物AE的男性占比均高于女性；年龄分布均在18岁以上；体重则多数集中在50~100 kg。CD19 CAR⁃T药物AE共累及到23类系统器官分类（system organ classification，SOC），主要集中在神经系统疾病和免疫系统疾病等，其中以细胞因子释放综合征（cytokine release syndrome，CRS）、免疫效应细胞相关性神经毒性综合征（immune effector cell⁃associated neurotoxicity syndrome，ICANS）最为常见。此外，还发现一些说明书中未列出的AE，如骨髓异常增生综合征（myelodysplastic syndromes，MDS）、急性肾损伤（acute kidney injury，AKI）和脓毒症等。结论 在CD 19 CAR⁃T药物的临床实践中，除需关注药物说明书中提及的AE外，还应注意可能发生的未提及的AE，如MDS、AKI和脓毒症等。

关键词: CD19 CAR-T药物, 不良反应, FAERS数据库, 数据挖掘

Abstract: Objective To analyze the adverse effects (AEs) of CD19 chimeric antigen receptor T (CAR⁃T) cell drugs on the market , so as to provide evidence for clinical treatment. Methods The United States Food and Drug Administration's adverse event reporting system (FAERS) database was used to obtain the baseline data and the AE results of four marketed CD19 CAR⁃T drugs from the first quarter of 2017 to the fourth quarter of 2023 after data retrieval, screening, deduplication, collation and analysis. The reporting odds ratio (ROR) and proportional ADR reporting ratio (PRR) were used to analyze and compare the AE results. Results A total of 5, 335 reports of 4 marketed CD19 CAR⁃T drugs included Axicabtagene ciloleucel (Axi⁃cel）, Tisagenleucel (Tisa⁃cel）, Brexucabtagene autoleucel (Brexu⁃cel) and Lisocabtagene maraleucel (Liso⁃cel) were obtained from the FAERS database. The proportion of the four CD19 CAR⁃T drugs in males was higher than that in females; the age distribution was above 18 years old; and the body weight was mostly concentrated in 50-100 kg. CD19 CAR⁃T drugs were involved in 23 types of system organ classification (SOC）, mainly focusing on neurological diseases and immune system diseases, among which cytokine release syndrome (CRS) and immune effector cell⁃associated neurotoxicity syndrome (ICANS) were the most common. In addition, some AEs not listed in the label were also found in this study, such as myelodysplastic syndromes (MDS）, acute kidney injury (AKI）, and sepsis. Conclusions In clinical practice, attention should also be paid to the possible unlisted AEs, such as MDS, AKI and sepsis, in addition to the AEs mentioned in the drug label. 

Key words: CD19 CAR-T drugs, Adverse effects, FAERS database, Data mining

中图分类号: 

  • R730.6