帕博利珠单抗致免疫检查点抑制剂相关肺炎临床及文献病例分析  

Immune checkpoint inhibitor-related pneumonitis caused by pembrolizumab:a case report and literature review

作　　者：闫雪莲[1] 黄茜[2] 葛楠 孙雯娟[1] 张波[1] 王凯 Yan Xuelian;Huang Qian;Ge Nan;Sun Wenjuan;Zhang Bo;Wang Kai(Department of Pharmacy,Peking Union Medical College Hospital,Chinese Academy of Medical Science,Beijing 100730,China;Department of Pharmacy,Beijing Shunyi Airport Hospital,Beijing 101318,China;Department of Geriatrics,Peking Union Medical College Hospital,Chinese Academy of Medical Science,Beijing 100730,China;Department of Pharmacy,Weifang No.2 People's Hospital,Shandong Province,Weifang 261000,China)

机构地区：[1]中国医学科学院北京协和医院药剂科,北京100730 [2]北京市顺义区空港医院药剂科,北京101318 [3]中国医学科学院北京协和医院老年医学科,北京100730 [4]山东省潍坊市第二人民医院药剂科,潍坊261000

出　　处：《药物不良反应杂志》2020年第11期631-637,共7页Adverse Drug Reactions Journal

摘　　要：目的探讨帕博利珠单抗致免疫检查点抑制剂相关肺炎(CIP)的临床特点。方法报道北京协和医院收治的1例帕博利珠单抗致CIP患者的诊治经过,并对该例以及检索PubMed、Embase、ScienceDirect和中国知网、维普、万方数据库(截至2019年10月1日)收集到的相关病例主要临床资料(性别、年龄、原发病、帕博利珠单抗用药情况、联合用药情况、CIP发生时间、临床症状、影像学检查结果、分级、临床处理及转归等)进行汇总分析。结果纳入分析的患者共33例,男性23例,女性10例;年龄44~91岁,中位年龄64岁;原发病为黑色素瘤者11例,肺腺癌9例,淋巴瘤4例,结肠癌3例,食管癌、乳腺癌、鼻咽癌、肺多形性癌、肺大细胞神经内分泌瘤、肺鳞状细胞癌各1例;单用帕博利珠单抗者30例,联用卡铂、培美曲塞者1例,联合放射治疗者2例。33例患者首次应用帕博利珠单抗至发生CIP的时间最短1 d,最长2年,中位发生时间为用药后12(4,16)周。CIP的主要症状包括呼吸困难(19例)、咳嗽咳痰(15例)、发热(9例)等;影像学检查多见磨玻璃影(17例)、肺部实变影(11例)及网格状高密度影(8例)。诊断CIP后,患者均停用帕博利珠单抗,29例给予糖皮质激素治疗,19例给予抗感染药物治疗,2例给予人免疫球蛋白治疗,1例给予英夫利昔单抗治疗。30例有临床转归描述的患者中24例好转,6例死亡;好转患者中有6例再次给予帕博利珠单抗,1例再次发生CIP。结论帕博利珠单抗致CIP临床表现及影像学特征缺乏特异性,用药后12周内应关注患者是否出现发热和呼吸道症状。大部分患者在CIP发生后可通过停药和加用糖皮质激素改善症状,但仍需警惕CIP潜在的致命风险。Objective To explore the clinical characteristics of immune checkpoint inhibitorrelated pneumonitis(CIP)caused by pembrolizumab.Methods We reported a case of CIP caused by pembrolizumab admitted in Peking Union Medical College Hospital and searched case reports on CIP caused by pembrolizumab in PubMed,Embase,ScienceDirect,CNKI,VIP,and Wanfang databases(as of October 1,2019).The main clinical data(gender,age,primary diseases,use of pembrolizumab,combination drugs,time to onset of CIP,symptoms,imaging results,CIP grade,and treatment and outcome)in all reported cases were collected and analyzed.Results A total of 33 patients were enrolled,including 23 males and 10 females,aged from 44 to 91 years with a median age of 64 years.The primary diseases in 11 cases were melanoma,in 9 cases were lung adenocarcinoma,in 4 cases were lymphoma,in 3 cases were colon cancer,and in 6 patients were esophageal cancer,breast cancer,nasopharyngeal cancer,pulmonary pleomorphic carcinoma,pulmonary large-cell neuroendocrine carcinoma,and lung squamous cell cancer,respectively.Thirty patients received pembrolizumab as monotherapy,1 patient received combination therapy of pembrolizumab with carboplatin and pemetrexed,and 2 patients received pembrolizumab combined with radiation therapy.Time to onset of CIP in the 33 patients was 1 day at the shortest and 2 years at the longest with a median time of 12(4,16)weeks.The symptoms of CIP mainly were dyspnea in 19 cases,cough and expectoration in 15 cases,and fever in 9 cases.The common radiological features were ground glass opacities in 17 cases,consolidations in 11 cases,and grid-like high-density shadow in 8 cases.After the diagnosis of CIP,all patients stopped using pembrolizumab.Twenty-nine patients were treated with glucocorticoids,19 patients received antibacterial therapy,2 patients received human immunoglobulin,1 patient received infliximab,and 2 patients did not receive any intervention.Of the 30 patients with known clinical outcomes,24 patients were improved and 6 died.Among the impro

关 键 词：抗肿瘤药 免疫类 肺炎 药物相关副作用和不良反应 帕博利珠单抗 

分 类 号：R969[医药卫生—药理学]