Risk analysis of neurological adverse events related to CAR T-cell therapy with brexucabtagene autoleucel based on the US FDA Adverse Event Reporting System
10.3760/cma.j.cn114015-20221226-01168
- VernacularTitle:基于美国FDA不良事件报告系统数据库CAR-T细胞疗法brexucabtagene autoleucel神经系统不良事件风险分析
- Author:
Na ZHAO
1
;
Xia YE
;
Zhiyan WANG
;
Chao LU
;
Fangyuan HU
;
Lei YUAN
Author Information
1. 中国人民解放军东部战区海军医院眼科，舟山 316000
- Publication Type:Journal Article
- Keywords:
Immunotherapy, adoptive;
Nervous system;
Drug toxicity;
Adverse event reporting system;
CAR T-cell therapy;
Brexucabtagene autoleucel
- From:
Adverse Drug Reactions Journal
2023;25(8):454-459
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the neurological adverse events (AE) associated to brexucabtagene autoleucel (brexu-cel) and their risk of occurrence.Methods:Neurological AE reports related to brexu-cel were collected through the US FDA Adverse Event Reporting System database from July 1, 2020 to September 31, 2022. The AEs were classified and counted according to the system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities (MedDRA) 24.1. The information component ( IC) method and the reporting odds ratio ( ROR) method were used to perform signal mining. AEs with ≥3 reports and a lower limit of 95% confidence interval ( CI) for IC>0 or that for ROR>1 were defined as positive risk signals. The proportion of patients who suffered fatal outcomes after experiencing neurological AEs related to brexu-cel was analyzed. Results:A total of 1 960 neurological AE reports related to brexu-cel were collected, involving 559 patients and 22 PTs. Fifteen positive signals (PT) were detected by using the IC and ROR methods. The top 5 PTs in the number of AE reports were immune effector cell-associated neurotoxicity syndrome (153 reports), altered mental status (32 reports), encephalopathy (29 reports), tremor (27 reports), and aphasia (25 reports); the top 5 PTs with the high signal intensity were immune effector cell-associated neurotoxicity syndrome ( IC=7.81, ROR=235.74), encephalopathy ( IC=4.74, ROR=26.96), aphasia ( IC=4.28, ROR=19.58), cerebral edema ( IC=3.35, ROR=10.24), and incontinence ( IC=3.04, ROR=8.22); incontinence (6 cases, IC=3.04, ROR=8.22) was not recorded in the drug instruction. Patients involved in 17 PTs, out of the 22 PTs, had fatal outcomes, and the proportion of deaths from immune effector cell-associated neurotoxicity syndrome was 18% (28/153). The PTs with a proportion of patient deaths >50% were unresponsive to stimuli (80%, 4/5), brain oedema (75%, 6/8), cerebrovascular accident (67%, 2/3), lethargy (60%, 3/5), and seizure (57%, 4/7). Conclusions:Neurological AEs related to brexu-cel are common, of which incontinence is not yet recorded in the drug instruction. The clinical outcomes of some AEs (unrespontive to stimulus, brain oedema, and lethargy) are poor and should be closely monitored.
