文章：

胃肠道感染和胃肠道出血是嵌合抗原受体T细胞治疗受者中被低估的严重不良事件：一项真实世界研究

Gastrointestinal infections and gastrointestinal haemorrhage are underestimated but serious adverse events in chimeric antigen receptor T-cell recipients: A real-world study

原文发布日期：2024-03-28 

英文摘要：

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. 

摘要翻译： 

嵌合抗原受体T细胞（CAR-T）疗法在血液恶性肿瘤患者中实现了持久缓解，然而治疗相关的多系统毒性反应仍常见。本研究利用美国食品药品监督管理局不良事件报告系统（FAERS），对2017年1月至2021年12月期间CAR-T相关胃肠道不良事件（GAEs）进行系统性分析。采用报告比值比（ROR）和信息成分（IC）进行不成比例性分析。在FAERS数据库105,087,611份报告中，共识别出1518例CAR-T相关GAEs报告。与完整数据库相比，23种GAEs（n=281，18.51%）在CAR-T治疗后呈现显著过度报告，其中11种GAEs（n=156，10.28%）与胃肠道感染相关，包括难辨梭菌结肠炎（n=44 [2.90%]，ROR=5.55）、肠道病毒感染（n=23 [1.52%]，ROR=20.02）和毛霉病（n=15 [0.99%]，ROR=3.09）。总体而言，11种胃肠道感染相关不良事件的致死率为29.49%，其中毛霉病死亡率高达60%。此外，23种过度报告的GAEs中有4种与出血相关，胃肠道出血的死亡率为73.17%。最终共鉴定出29种致死性GAEs。这些发现有助于临床医生早期警惕那些罕见但致命的GAEs，从而降低严重毒性反应风险。

原文链接：

Gastrointestinal infections and gastrointestinal haemorrhage are underestimated but serious adverse events in chimeric antigen receptor T-cell recipients: A real-world study