免疫相关的不良事件（irAEs）是由免疫检查点抑制剂（ICIs）使用引起的毒性反应。即使停止治疗并使用免疫抑制和免疫调节剂，这些副作用在一些患者中仍然持续存在。对于慢性irAEs的了解甚少，它们被认为是罕见的。我们进行了系统回顾，以描述文献中报道的非内分泌慢性irAEs的特征和管理方法。在Ovid MEDLINE和Embase数据库中搜索了使用ICIs治疗的实体癌症成年患者报告的慢性（>12周）非内分泌irAEs。收集了患者、治疗和毒性数据。在识别的6843篇文章中，符合纳入标准的有229个研究，涵盖了323名患者。患者的中位年龄为65岁（IQR 56-72岁），男性占58%。大多数患者（75%）有转移性疾病，43%的患者的原发癌症部位为黑色素瘤，31%为非小细胞肺癌。最常用的ICIs是pembrolizumab（24%）和nivolumab（37%）。患者经历的慢性irAEs中，风湿病学占20%，神经学占19%，胃肠学占16%，皮肤学占14%。irAE持续的中位时间为180天（范围84-2370天），30%的患者出现持续症状或需要继续治疗。超过半数（52%）的患者患有持续超过6个月的慢性irAEs。60%的患者永久停用ICI，76%的患者需要口服和/或静脉注射类固醇。这是文献中首次对ICIs治疗后中度/重度慢性非内分泌irAEs进行系统回顾和报道。这些毒性反应持续数月至数年，大多数患者需要停用治疗并开始免疫抑制治疗。需要进一步研究来更好地了解慢性irAEs，考虑到ICIs的广泛使用和它们在（新）辅助治疗中的整合，这些反应可能具有重要的临床意义。 ©作者（或其雇主）2023年。在CC BY-NC下允许重复使用。禁止商业再利用。由BMJ出版。

Immune-related adverse events (irAEs) are toxicities resulting from use of immune checkpoint inhibitors (ICIs). These side effects persist in some patients despite withholding therapy and using immunosuppressive and immune-modulating agents. Little is known about chronic irAEs and they are felt to be rare. We performed a systematic review to characterize non-endocrine chronic irAEs reported in the literature and describe their management. Ovid MEDLINE and Embase databases were searched for reports of adult patients with solid cancers treated with ICIs who experienced chronic (>12 weeks) non-endocrine irAEs. Patient, treatment and toxicity data were collected. Of 6843 articles identified, 229 studies including 323 patients met our inclusion criteria. The median age was 65 (IQR 56-72) and 58% were male. Most patients (75%) had metastatic disease and the primary cancer site was melanoma in 43% and non-small cell lung cancer in 31% of patients. The most common ICIs delivered were pembrolizumab (24%) and nivolumab (37%). The chronic irAEs experienced were rheumatological in 20% of patients, followed by neurological in 19%, gastrointestinal in 16% and dermatological in 14%. The irAE persisted for a median (range) of 180 (84-2370) days and 30% of patients had ongoing symptoms or treatment. More than half (52%) of patients had chronic irAEs that persisted for >6 months. The ICI was permanently discontinued in 60% of patients and 76% required oral and/or intravenous steroids. This is the first systematic review to assess and report on moderate/severe chronic non-endocrine irAEs after treatment with ICI in the literature. These toxicities persisted for months-years and the majority required discontinuation of therapy and initiation of immunosuppression. Further research is needed to better understand chronic irAEs, which hold potential substantial clinical significance considering the expanded use of ICIs and their integration into the (neo)adjuvant settings.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.