基于真实世界的研究——646例肿瘤患者使用免疫检查点抑制剂相关不良反应的临床特征

目的 探讨免疫检查点抑制剂（ICI）在临床应用中的免疫相关不良事件（irAE）发生情况及临床特征。方法 回顾性分析2020年5月—2022年6月接受PD-1和PD-L1治疗的晚期恶性肿瘤患者646例，观察并记录治疗期间irAEs的发生情况，包括发生率、发生时间、分级等。结果 646例患者中，259例患者共发生370次irAEs，发生率为40.1%。1、2级不良反应266次（71.9%），3级以上不良反应104次（28.1%）。irAEs可累及全身各个器官系统，其中以皮肤毒性（15.6%）最常见。61例（23.6%）患者发生多系统irAEs。年龄≤65岁，联合用药，使用卡瑞利珠单抗、信迪利单抗、帕博利珠单抗的患者更易发生多系统irAEs。血液系统毒性、肝脏毒性、心血管毒性发生在早期，平均发生时间为治疗3个疗程内。年龄>65岁、合并自身免疫性疾病的患者行ICIs治疗可获得同等临床效益，具有良好的安全性。irAEs发生情况与患者的性别、年龄、合并症、用药方案、肿瘤类型、ICIs种类、免疫药物类型无关（P>0.05），与用药疗程有关（P<0.05）。结论 ICIs临床应用广泛，严重不良反应发生率低，有一定的安全性，但不良反应可累及全身各个器官系统，应做好各类irAEs的早期识别、诊断及治疗。

A real world research: the clinical characteristics of immune-related adverse events in 646 cases

Objective To investigate the incidence and clinical characteristics of immune-related adverse events (irAE) in the clinical application of immune checkpoint inhibitors (ICIs).Methods 646 patients with advanced malignant tumors who were treated by PD-1 and PD-L1 inhibitors between May 2020 and June 2022 were retrospectively analyzed in this study. The occurrence of their irAEs during treatment was observed and recorded, including the incidence rate, occurrence time, grade, etc.Results A total of 370 irAEs occurred in 259 of 646 patients, with an incidence rate of 40.1%. There were 266 (71.9%) irAEs of grade 1 and 2, and 104 (28.1%) irAEs of grade 3 or higher grade. The irAEs could involve all organs and systems, among which skin toxicities (15.6%) were the most common. 61 (23.6%) patients experienced multisystem irAEs. Patients with ≤65 years of age, drug combination, camrelizumab, sintilimab, or pembrolizumab were more likely to have multisystem irAEs. Hematological toxicities, hepatic toxicities, and cardiotoxicity occurred in the early time, averagely within 3 courses of treatment. Patients >65 years old and complicated with autoimmune diseases could also achieve clinical benefits with a good safety. Though incidence of irAEs was not associated with gender, age, complications, therapeutic regimens, tumor types, types of ICIs, and types of immune drugs (P>0.05), it was associated with the course of treatment (P<0.05).Conclusion ICIs are widely used in clinical practice, with a low incidence rate of serious adverse events and a relative safety. However, their adverse reactions can involve various organs and systems throughout the body, so it is important to get early identification, diagnosis and treatment of irAEs for these patients.