Department of Hematology, Institute of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
Cancer Gene Ther. 2024 May;31(5):710-720. doi: 10.1038/s41417-024-00752-0. Epub 2024 Mar 28.
Chimeric antigen receptor T-cell (CAR-T) therapy has achieved durable response in patients with hematological malignancies, however, therapy-associated multisystem toxicities are commonly observed. Here, we systematically analyzed CAR-T-related gastrointestinal adverse events (GAEs) using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) between January 2017 and December 2021. Disproportionality analyses were performed using reporting odds ratios (ROR) and information component (IC). Among 105,087,611 reports in FAERS, 1518 CAR-T-related GAEs reports were identified. 23 GAEs (n = 281, 18.51%) were significantly overreported following CAR-T therapy compared with the full database, of which 11 GAEs (n = 156, 10.28%) were associated with gastrointestinal infections (GI), such as clostridium difficile colitis (n = 44 [2.90%], ROR = 5.55), enterovirus infection (n = 23 [1.52%], ROR = 20.02), and mucormycosis (n = 15 [0.99%], ROR = 3.09). Overall, the fatality rate of 11 GI-related AEs was 29.49%, especially mucormycosis causing substantial mortality with 60%. In addition, 4 of 23 overreported GAEs were related to haemorrhage and the mortality of gastrointestinal haemorrhage was 73.17%. Lastly, 29 death-related GAEs were identified. These findings could help clinicians early alert those rarely reported but lethal GAEs, thus reducing the risk of severe toxicities.
嵌合抗原受体 T 细胞(CAR-T)疗法在血液系统恶性肿瘤患者中实现了持久的缓解,但治疗相关的多系统毒性也很常见。在这里,我们使用美国食品和药物管理局不良事件报告系统(FAERS),在 2017 年 1 月至 2021 年 12 月期间,系统地分析了与 CAR-T 相关的胃肠道不良事件(GAEs)。采用报告比值比(ROR)和信息量(IC)进行了比例失调分析。在 FAERS 的 105087611 份报告中,确定了 1518 份与 CAR-T 相关的 GAEs 报告。23 种 GAEs(n=281,18.51%)在 CAR-T 治疗后显著高于全数据库,其中 11 种 GAEs(n=156,10.28%)与胃肠道感染(GI)相关,如艰难梭菌结肠炎(n=44 [2.90%],ROR=5.55)、肠道病毒感染(n=23 [1.52%],ROR=20.02)和毛霉菌病(n=15 [0.99%],ROR=3.09)。总的来说,11 种与 GI 相关 AE 的死亡率为 29.49%,特别是毛霉菌病死亡率高达 60%。此外,23 种过度报告的 GAEs 中有 4 种与出血有关,胃肠道出血的死亡率为 73.17%。最后,确定了 29 例与死亡相关的 GAEs。这些发现可以帮助临床医生早期警惕那些罕见但致命的 GAEs,从而降低严重毒性的风险。
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