免疫检查点抑制剂PD-1免疫相关不良反应的临床分析

Clinical analysis of immune-related adverse events of PD-1 immune checkpoint inhibitors

目的探讨程序性细胞死亡蛋白-1(PD-1)免疫检查点抑制剂(ICI)临床应用中的免疫相关不良反应(irAE)及临床处理。方法回顾性分析自2019年1月至12月共194例/473次接受PD-1治疗恶性肿瘤的患者,观察治疗期间患者发生的irAE,包括不良反应的类别、分级、发生时间、持续时间、处理方案、预后等指标。结果 194例患者中,83例发生irAE,发生率为42.8%,其中13例(6.7%)同时出现累及多个系统的不良反应。发生的不良反应中1、2级不良反应75例(38.7%),3级以上不良反应8例(4.1%),3级以上不良反应分别为3级肝毒性3例、3级结肠炎1例、3级皮肤毒性2例、4级肺炎1例、5级肺炎死亡1例。7例患者经激素冲击治疗、维持治疗和对症治疗后不良反应完全缓解,其中5例继续使用PD-1单抗、2例停用,1例患者因免疫性肺炎观察延迟导致全身多器官功能衰竭死亡。irAE发生在不同系统或器官的发生时间、持续时间各有不同。结论 PD-1在临床应用中是安全的,3级以上不良反应发生率低,及时发现、早期激素治疗有效。

Objective To explore the immune-related adverse events(irAEs) of programmed cell death protein(PD-1) immune checkpoint inhibitors(ICI) in clinical application,and to discuss the clinical treatment.Methods The clinical data of a total of 194 patients with malignant tumor,who received PD-1 ICI(473 times in total) from January 2019 to December 2019,were retrospectively analyzed. The incidences of irAEs,including the type,grade,occurrence time,duration,treatment plan,prognosis and other indicators,during treatment course were calculated. Results Among 194 patients,83(42.8%) developed irAEs,of them 13(6.7%)simultaneously appeared adverse events involving multiple systems. Among them,75 patients(38.7%) had adverse reactions of grade Ⅰ-Ⅱ,8 patients(4.1%) had adverse reactions of ≥grade Ⅲ. The adverse reactions of≥grade Ⅲ included grade Ⅲ liver toxicity(n=3),grade Ⅲ colitis(n=1),grade Ⅲ skin toxicity(n=2),grade Ⅳpneumonia(n=1) and death due to grade V pneumonia(n=1). The adverse reactions were completely relieved after hormone shock therapy,maintenance therapy and symptomatic treatment in 7 patients,among them 5 patients kept receiving PD-1 monoclonal antibody,2 patients stopped using PD-1 monoclonal antibody,and one patient died of systemic multiple organ failure as the observation of immune pneumonia was delayed. The time of occurrence and the duration of irAEs were different from system to system as well as from organ to organ. Conclusion The use of PD-1 immune checkpoint inhibitors is clinically safe,the incidence of ≥gradeⅢ adverse reactions is low,and for which timely detection and early hormone therapy are important and effective.(J Intervent Radiol,2021,30: 29-33)