CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
胃肠道感染与胃肠道出血是 CAR-T 细胞受者被低估但严重的不良事件：一项真实世界研究
英文原题：Gastrointestinal infections and gastrointestinal haemorrhage are underestimated but serious adverse events in chimeric antigen receptor T-cell recipients: A real-world study.
查看英文原题
Gastrointestinal infections and gastrointestinal haemorrhage are underestimated but serious adverse events in chimeric antigen receptor T-cell recipients: A real-world study.
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中文摘要
CAR-T 细胞治疗已使血液系统恶性肿瘤患者获得持久应答，但治疗相关多系统毒性较常见。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），系统分析了2017年1月至2021年12月CAR-T 相关胃肠道不良事件（GAE）。研究采用报告比值比（ROR）和信息成分（IC）进行不均衡性分析。在FAERS的105,087,611份报告中，识别出1,518份CAR-T 相关GAE报告。与整个数据库相比，CAR-T 治疗后有23种GAE（n=281，占18.51%）报告显著过多；其中11种（n=156，占10.28%）与胃肠道感染有关，例如艰难梭菌结肠炎（n=44，占2.90%；ROR=5.55）、肠道病毒感染（n=23，占1.52%；ROR=20.02）和毛霉菌病（n=15，占0.99%；ROR=3.09）。11种胃肠道感染相关不良事件的总体病死率为29.49%，其中毛霉菌病死亡负担尤为突出，病死率达60%。
此外，23种报告过多的GAE中有4种与出血有关，胃肠道出血病死率为73.17%。最后，研究识别出29种与死亡相关的GAE。这些发现有助于临床医生及早警惕虽少见但致命的GAE，从而降低严重毒性风险。
展开英文摘要原文
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.
论文信息
- 作者
- Song Z、Wang Y、Liu P、Geng Y、Liu N、Chen J、Yang J
- 第一作者单位
- Department of Hematology, Institute of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.China
- 通讯作者单位
- Department of Hematology, Institute of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. yangjianmin123@smmu.edu.cn.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Cancer gene therapy2024 May
- 原文标识
- PubMed 38548883 · DOI 10.1038/s41417-024-00752-0