免疫检查点抑制剂治疗非小细胞肺癌产生免疫相关不良反应和肺炎的特点及其危险因素分析

Characteristics and risk factors of immune-related adverse events and pneumonitis associated with immune checkpoint inhibitors in the treatment of non-small cell lung cancer

目的:探讨免疫检查点抑制剂(ICI)治疗非小细胞肺癌(NSCLC)产生的免疫相关不良反应(irAE)及ICI相关肺炎(ICI-P)的特点及其危险影响因素。方法:回顾性分析2019年1月到2021年12月间在山西白求恩医院胸部肿瘤科接受至少1次ICI治疗的114例NSCLC患者的一般性资料和临床特征的基线特征、治疗细节和发生irAE、ICI-P的数据,分析患者临床特征与irAE及ICI-P的关系,分析ICI-P发生的危险因素。观察ICI-P患者临床特点和治疗效果。结果:114例接受ICI治疗的NSCLC患者中有48例(42.11%)发生68次irAE,整体和严重irAE的发生率分别是59.65%、9.65%;从高到低排列发生率(仅列出前四位):消化系统>呼吸系统>皮肤>内分泌系统;使用信迪利单抗>度伐利尤单抗>卡瑞利珠单抗=帕博利珠单抗;临床特征中的年龄与irAE发生有关联。15例患者发生ICI-P,整体发生率为13.16%,占irAE患者的31.25%,其中4例为重症,占irAE数的8.33%、ICI-P数的26.66%;发生于联合治疗的多于单药治疗(73.33%vs 26.67%),药物使用以信迪利单抗的发生率为最高(占ICI-P数的60%);吸烟史为ICI-P的危险因素。多数ICI-P患者都出现普通呼吸道症状,重症者均为老年吸烟者,其症状较重,且影像学见纤维化和磨玻璃状影;仅1例未停用ICI,余均暂停和推迟使用ICI并接受皮质激素治疗,疗效均良好。结论:ICI治疗NSCLC中irAE发生率较高且以高龄患者居多,约1/3的irAE患者发生ICI-P,约1/4的ICI-P为重症,吸烟史是发生ICI-P的危险因素。

Objective:To investigate the clinical characteristics and risk factors of immune-related adverse events(irAEs)and immune checkpoint inhibitor-related pneumonitis(ICI-P)in non-small cell lung cancer(NSCLC)patients treated with immune checkpoint inhibitors(ICIs).Methods:The baseline characteristics,treatment details and data on the occurrence of irAE and ICI-P from general information and clinical characteristics of 114 NSCLC patients who received at least 1 ICI treatment at the Department of Thoracic Oncology,Shanxi Bethune Hospital during January 2019 and December 2021 were retrospectively analyzed.The relationship between patients'clinical characteristics and irAE as well as ICI-P was investigated,and the risk factors for the occurrence of ICI-P were also analyzed.Moreover,the characteristics and treatment outcomes of patients with ICI-P were also observed.Results:There were 68 irAEs occurred in 48(42.11%)out of 114 NSCLC patients treated with ICIs,with the incidences of overall irAE and severe irAEs of 59.65% and 9.65%,respectively.The organs associated with the incidence of irAE in the descending order(only the top four are listed)were gastrointestinal system>respiratory system>skin>endocrine system;and the ICIs associated with the incidence of irAE were sindilizumab>dulcolizumab>carrelixumab=Pabrolizumab.Age in clinical characteristics was associated with the occurrence of irAE.15 patients developed ICI-P,with an overall incidence of 13.16%,accounting for 31.25% of all irAE patients,of whom 4 were severe,accounting for 8.33% of the number of irAE and 26.66% of the number of ICI-P.The incidence of ICI-P was higher in patients with combination therapy than those with monotherapy(73.33%vs 26.67%),and the incidence of ICI-P was the highest in patients treated with Sindilizumab(60% of ICI-P cases).A history of smoking was a risk factor for ICI-P.Most of the patients with ICI-P presented with common respiratory symptoms,and all of the severe cases were elderly smokers with severe symptoms and fibrosis or a ground glass appearance on imaging.Only one case did not discontinue ICI,and the rest suspended or delayed ICI and received corticosteroid therapy with good outcomes.Conclusion:The incidence of irAE in ICI-treated NSCLC is high and predominantly in elderly patients.About 1/3 of patients with irAE develop ICI-P and about 1/4 of ICI-P is severe.A history of smoking is a risk factor for the development of ICI-P.