免疫检查点抑制剂相关的严重罕见毒性研究进展

Progress in the study of severe and rare toxicity related to immune checkpoint inhibitors

目的免疫检查点抑制剂(ICI)对许多恶性肿瘤显示出良好的疗效。随着ICI临床应用日益增多,免疫相关不良事件(irAEs)的报道越来越多。然而,国内ICI应用于临床时间较短,临床医护人员对一些严重不良反应的认识并不充分,尤其对一些罕见严重不良反应认识不足。方法应用PubMed和中国知网数据库进行检索,分别以"免疫检查点抑制剂、irAEs、严重罕见毒性、处理""Immune checkpoint inhibitors,irAEs,severe and rare toxicity,treatment"为关键词,检索2015-2021年发表的相关文献。纳入标准:irAEs;严重罕见毒性;严重罕见的毒性处理。排除标准:综述文献;重复发表的文献。最终纳入英文文献46篇,中文文献2篇。结果irAEs可发生在任何器官系统,以皮肤、消化道、内分泌、肺等较为常见,而其他器官系统如神经系统、心脏、肾脏、眼等却比较罕见。绝大多数irAEs可用糖皮质激素处理。irAEs具有非特异和不典型的特性;当与其他抗肿瘤药物联合使用时,irAEs难以鉴别。结论虽然irAEs多为轻中度,但若不及时诊断和处理,可能会导致严重后果。因此,早期诊断和及时处理对缓解irAEs、避免严重irAEs的发生十分重要。

Objective Immune checkpoint inhibitor(ICI) has shown good effects on many malignant tumors.With the increasing use of ICI in clinical, more and more immune-related adverse events(irAEs) have been reported.However, ICI has been used for a relatively short time in China, and some severe adverse reactions especially some rare and severe adverse reactions are not fully understood by clinical medical staff.Therefore, we summarize these adverse events in this review.Methods The PubMed and CNKI database were used to search for relevant literature from 2015 to 2021,using "immune checkpoint inhibitor, immune-related adverse events, severe and rare toxicity, and management" as keywords.Inclusion criteria: covered immune-related adverse events, severe and rare, treatment of severe and rare toxicity.Exclusion criteria included review literature and duplicate review literature.Finally, 46 articles in English and 2 articles in Chinese were included.Results IrAEs can occur in any organs, commonly in the skin, gastrointestinal system, endocrine system, and lungs, but less commonly in other organs such as the nervous system, cardiac, kidney, and eye etc.Most irAEs can be treated with glucocorticoids.IrAEs are non-specific and atypical.IrAEs are difficult to identify when used in combination with other anti-tumor drugs.Conclusions Although irAEs are usually mild to moderate, if not diagnosed and treated promptly, serious consequences may result.Therefore, early diagnosis and timely treatment are very important to alleviate irAEs and avoid the occurrence of fatal irAEs.