Guo Zihan, Ding Yunlan, Wang Mengmeng, Zhai Qing, Liu Jiyong, Du Qiong
Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Pharmaceuticals (Basel). 2024 Aug 5;17(8):1025. doi: 10.3390/ph17081025.
In this study, we compared the similarities and differences in adverse events (AEs) among CAR T-cell products through signal mining via the FDA Adverse Event Reporting System (FAERS) and identified unknown AEs to provide a reference for safe clinical medication. Data from the FAERS database spanning from the fourth quarter of 2017 to the first quarter of 2024 were extracted. Signals were identified using the reporting odds ratio (ROR) method and the Medicines and Healthcare Products Regulatory Agency (MHRA) method. A total of 11,386 AE reports related to six CAR T-cell products were selected. The top three categories of AEs reported were nervous system disorders, immune system disorders, and general disorders and administration site conditions. However, there were variations in the AE spectra among the different CAR T-cell products. The BCMA-targeting drugs idecabtagene vicleucel (Ide-cel) and ciltacabtagene autoleucel (Cilta-cel) were found to be associated with parkinsonism, which were not observed in CD19-targeting drugs. Tisagenlecleucel (Tisa-cel) and axicabtagene ciloleucel (Axi-cel) exhibited cerebrovascular accident-related AEs, graft versus host disease, and abnormal coagulation indices. Cilta-cel was associated with cerebral hemorrhage, intracranial hemorrhage, cranial nerve disorder, and facial nerve disorder. Cardiopulmonary toxicity, including hypoxia, tachypnoea, cardiorenal syndrome, and hypotension, exhibited strong signal intensities and considerable overlap with CRS. The number of positive signals for cardiopulmonary toxicity associated with drugs targeting CD-19 is greater. Clinicians should assess patients prior to medication and closely monitor their vital signs, mental status, and laboratory parameters during treatment.
在本研究中,我们通过美国食品药品监督管理局不良事件报告系统(FAERS)进行信号挖掘,比较了嵌合抗原受体(CAR)T细胞产品之间不良事件(AE)的异同,并识别出未知的不良事件,为临床安全用药提供参考。提取了FAERS数据库中2017年第四季度至2024年第一季度的数据。使用报告比值比(ROR)方法和英国药品和保健品管理局(MHRA)方法识别信号。共选择了11386份与六种CAR T细胞产品相关的AE报告。报告的AE前三大类别为神经系统疾病、免疫系统疾病以及全身疾病和给药部位情况。然而,不同CAR T细胞产品的AE谱存在差异。发现靶向B细胞成熟抗原(BCMA)的药物idecabtagene vicleucel(Ide-cel)和西达基奥仑赛(ciltacabtagene autoleucel,Cilta-cel)与帕金森症有关,而在靶向CD19的药物中未观察到这种情况。替雷利珠单抗(Tisagenlecleucel,Tisa-cel)和阿基仑赛(axicabtagene ciloleucel,Axi-cel)出现了与脑血管意外相关的AE、移植物抗宿主病和凝血指标异常。Cilta-cel与脑出血、颅内出血、脑神经疾病和面神经疾病有关。心肺毒性,包括缺氧、呼吸急促、心肾综合征和低血压,表现出强烈的信号强度,且与细胞因子释放综合征(CRS)有相当程度的重叠。与靶向CD-19的药物相关的心肺毒性阳性信号数量更多。临床医生在用药前应评估患者,并在治疗期间密切监测其生命体征、精神状态和实验室参数。