帕博利珠单抗致老年晚期肺癌患者免疫相关不良事件的发生情况及临床特征分析

Analysis of the occurrence and clinical characteristics of immune‑related adverse events caused by pembrolizumab in elderly patients with advanced lung cancer

目的了解帕博利珠单抗(PEM)致老年晚期肺癌患者免疫相关不良事件(irAE)的发生情况和临床特征。方法研究对象选自2020年8月至2022年7月在内蒙古医科大学附属医院接受PEM治疗(用法用量均为200 mg静脉滴注、1次/21 d,21 d为1个周期)的老年晚期肺癌患者。检索医院电子病历信息系统,收集符合纳入标准患者的病历资料,记录患者基本情况、肺癌病理类型、临床分期、是否联合化疗以及irAE发生时间、临床表现、干预及预后等临床数据进行回顾性分析,并根据美国国家癌症研究所不良事件通用术语标准5.0版进行irAE分级。结果纳入分析的患者共100例,其中22例(22%)发生irAE。22例患者中,男性19例,女性3例;年龄61~90岁;肺鳞状细胞癌15例,肺腺癌7例;临床分期为Ⅲ期者4例,Ⅳ期18例;PEM单药治疗者1例,联合化疗者21例。22例患者共发生irAE 28例次(发生1种irAE者19例,2、3、4种者各1例),其中皮肤irAE 10例次(1级3例次,2级3例次,3级4例次),免疫相关性肺炎8例次(1级1例次,2级7例次),内分泌系统irAE 7例次(甲状腺功能减退1级1例次、2级3例次,1级肾上腺皮质功能减退1例次,1级血糖升高1例次,4级垂体炎1例次),免疫相关性肝炎2例次(1级1例次,3级1例次),免疫相关性心肌炎1例次(3级)。28例次irAE发生时间最短者为初始用药当日,最长为第17个周期用药后20 d,22例次发生在用药第1~8个周期之间。发生irAE后,5例患者停用PEM,多数接受激素和/或对症治疗,20例患者治愈或自愈,1例部分痊愈,1例未改善。结论老年晚期肺癌患者应用PEM后可发生皮肤、肺、内分泌系统、肝脏和心脏irAE,多在用药第1~8个周期之间出现,多为1和2级,停药并给予激素和/或对症处理,预后较好。

Objective To investigate the occurrence and clinical characteristics of immune‑related adverse events(irAEs)caused by pembrolizumab(PEM)in elderly patients with advanced lung cancer.Methods The subjects were selected from the elderly patients with advanced lung cancer who received PEM therapy(200 mg was given by intravenous infusion once every 21 days and 21 days was a cycle)in the Affiliated Hospital of Inner Mongolia Medical University from August 2020 to July 2022.The medical records of patients meeting the inclusion criteria were collected through the Hospital Electronic Medical Record Information System,the clinical data such as patients′basic information,pathological type of lung cancer,clinical stage,whether or not combination with chemotherapy,the occurrence time of irAEs,clinical manifestations,intervention,and prognosis were recorded and analyzed retrospectively.The irAEs were graded according to the Common Terminology Criteria for Adverse Event(CTCAE)Version 5.0 developed by the National Cancer Institute of the United States.Results A total of 100 patients were enrolled in the analysis,of which 22(22%)patients developed irAEs.Among the 22 patients,19 were male and 3 were female,aged from 61 to 90 years,including 15 lung squamous cell carcinomas and 7 lung adenocarcinomas.There were 4 patients with clinical stageⅢand 18 patients with stageⅣ;one patient received PEM monotherapy and 21 patients received PEM combined with chemotherapy.A total of 28 cases of irAEs occurred in 22 patients(19 cases of 1 type of irAE,1 case of 2,3,and 4 types of irAE each),including 10 cases of skin irAEs(3 in grade 1,3 in grade 2,and 4 in grade 3),8 cases of immune‑related pneumonitis(1 in grade 1,7 in grade 2),7 cases of irAEs involving the endocrine system(1 case of hypothyroidism in grade 1,3 cases of hypothyroidism in grade 2,1 case of adrenocortical dysfunction in grade 1,1 case of hyperglycemia in grade 1,and 1 case of pituitary inflammation in grade 4),2 cases of immune‑associated hepatitis(1 in grade 1,1 in grade 3),1 case of ICI‑related myocarditis in grade 3.The shortest occurrence time of the 28 cases of irAEs was on the day of initial medication,the longest was 20 days after the 17th cycle of medication,and 22 cases occurred between the 1st to 8th cycles of medication.After the occurrence of irAEs,5 patients discontinued PEM and most received hormone and/or symptomatic treatment.Twenty patients were cured or self‑healed,1 partially recovered,and 1 was not improved.Conclusions Elderly patients with advanced lung cancer who receive PEM may experience skin,lung,endocrine system,liver,and heart irAEs,mostly occurring between the 1st to 8th cycles of medication,mostly in grades 1 and 2.Discontinuation of medication and hormone and/or symptomatic treatment can lead to a better prognosis.