免疫相关不良事件在肺癌中发生和结局的真实世界研究

A Real-world Study on the Incidence and Outcome of Immune-related Adverse Events in Lung Cancer Patients

背景与目的免疫相关不良事件(immune-related adverse events,ir AEs)常发生于免疫检查点抑制剂应用的患者,但关于肺癌中ir AEs发生和结局的国内证据相对缺乏。本研究旨在评估中国肺癌患者接受免疫治疗后ir AEs的发生和转归。方法纳入2018年1月-2021年9月在复旦大学附属华东医院接受过至少1次免疫检查点抑制剂治疗的肺癌患者的临床和随访资料,通过统计描述、Kaplan-Meier等方法分析ir AEs总体发生情况及各类ir AEs的发生与结局。结果共纳入135例患者,106例(78.5%)至少发生一种ir AEs,首次发生的中位时间为28 d。多数ir AEs发生于治疗早期,多为轻-中度、可恢复。57例(42.2%)患者死亡;严重ir AEs致死率为12.6%(n=17),其中7例(41.2%)死于肺炎。整体人群的中位无进展生存期(progression-free survival,PFS)为505 d(95%CI:352-658),中位总生存期(overall survival,OS)为625 d(95%CI:491-759)。发生任一ir AEs患者的PFS长于治疗未发生者(中位PFS分别为533d和179d,P=0.037;HR=0.57);发生皮肤毒性者的OS长于未发生者(中位OS分别为797d和469d,P=0.006;HR=0.70)。结论真实世界中肺癌患者ir AEs普遍发生,其中肺炎为最常见的致死性ir AEs,发生ir AEs患者群体存在PFS上的优势。

Background and objective Immune-related adverse events(irAEs)are commonly occurred in patients treated with immune checkpoint inhibitors.However,evidence of irAEs derived from the Chinese population is relatively lacking.The aim of this study was to investigate the incidence and outcomes of irAEs in Chinese patients with lung cancer after receiving immune checkpoint inhibitors(ICIs).Methods Clinical and follow-up data from lung cancer patients who received at least one time of ICIs from January 2018 to September 2021 at Huadong Hospital,Fudan University were included.Statistical descriptions and Kaplan-Meier method were used to analyze the overall incidence of irAEs,as well as the incidence and outcomes of each type of irAEs.Results 135 patients were included in the study.106 patients(78.5%)presented at least one type of irAEs,and the median time to first irAEs onset was 28 d.Most irAEs occurred at early time after treatment,and most irAEs were mild-moderate and reversible.57 patients(42.2%)died at the study cutoff.The mortality rate of severe irAEs was 12.6%(n=17),and among them 7 patients(41.2%)died of pneumonitis.The median progression-free survival(PFS)and overall survival(OS)time of the total population was 505 d(95%CI:352-658)and 625 d(95%CI:491-759),respectively.Patients who presented any irAEs achieved a longer PFS than those who did not(median PFS:533 d vs 179 d,P=0.037,HR=0.57),while patients who presented skin toxicities achieved a longer OS than patients who did not(median OS:797 d vs 469 d,P=0.006,HR=0.70).Conclusion In real-world settings,irAEs in lung cancer patients were commonly observed,with pneumonitis as the most common fatal irAEs.In addition,patients who presented any irAEs may tend to achieve a longer PFS.