中国肺癌患者应用程序性细胞死亡蛋白1抑制剂相关的心肌炎病例分析  

Case analysis of programmed cell death protein-1 inhibitor-related myocarditis in Chinese patients with lung cancer

作　　者：晋月萍[1] 尚楠[1] 郭阳[1] Jin Yueping;Shang Nan;Guo Yang(Department of Pharmacy,The First Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学第一医院药学部,太原030001

出　　处：《中华心力衰竭和心肌病杂志（中英文）》2022年第1期18-26,共9页Chinese Journal of Heart Failure and Cardiomyopathy

摘　　要：目的了解中国非小细胞肺癌(NSCLC)患者应用程序性细胞死亡蛋白1(PD-1)抑制剂后出现免疫相关心肌炎的临床特点及发病规律。方法检索中国生物医学文献数据库、中国知识资源总库(中国知网)、中国科技期刊数据库(维普网)、万方数据库及PubMed、Embase等数据库中收录的中国NSCLC患者应用PD-1抑制剂后出现免疫相关心肌炎的病例报道,检索时限为建库至2021年12月。在排除重复文献或病例后对纳入文献中患者的相关信息进行提取,使用EXCEL 2013软件进行数据整理、分析。结果共纳入14篇文献,英文6篇,中文8篇,涉及患者14例,使用的PD-1抑制剂包括纳武利单抗2例,帕博利珠单抗2例,特瑞普利单抗2例,信迪利单抗2例,卡瑞利珠单抗4例,替雷利珠单抗2例。男性8例,女性6例,年龄分布为50~82岁,平均年龄67岁。肺癌类型中腺癌8例,鳞癌5例,1例未明确NSCLC类型。多数(13例,占92.8%)患者心肌炎发生在使用PD-1抑制剂的前3周期内。11例记录了末次用药与心肌炎发生的间隔时间,范围为1~19天,中位数(四分位数间距)为6(4,15)天。最常见的临床症状为呼吸困难(7例),其次为肌痛(6例),乏力(5例)。除了心肌炎,其他免疫相关不良反应包括肌炎(5例),重症肌无力(5例),肝炎(5例)。14例均检测了心肌肌钙蛋白I或T,其数值均高于各自参考值范围上限。11例心电图异常,包括ST-T改变(7例)、完全性右束支传导阻滞(5例),室性期前收缩(3例)、室性心动过速(3例)。有13例描述了超声心动图检查结果,其中,6例记录左心室射血分数(LVEF)水平,仅2例LVEF<50%,其余4例LVEF在51%~63%。仅4例患者行心脏磁共振检查,其中2例提示心肌炎性改变,2例未见异常。所有患者在诊断心肌炎后均使用了糖皮质激素治疗,最常用甲基强的松龙(甲强龙)静脉应用,起始剂量不等,4例患者联合使用丙种球蛋白。14例患者中有3例因心肌炎死亡(病死率为21.4%)Objective To investigate the clinical characteristics and pathogenesis of immune-related myocarditis in Chinese patients with non-small cell lung cancer(NSCLC)after application of programmed cell death protein 1(PD-1)inhibitor.Method Databases such as CBM,VIP,CNKI,Wanfang database,PubMed,and Embase database were searched for the case reports of myocarditis associated with PD-1 inhibitors from the inception to December 2021.After eliminating literature and cases,relavant informations of included cases were extracted,and data was sorted and analyzed by using of EXCEL 2013 software.Results A total of 14 case reports and patients with NSCLC were enrolled,including 2 cases with nivolumab,2 cases with pembrolizumab,2 cases with toripalimab,2 cases with sintilimab,4 cases with camrelizumab and 2 cases with tislelizumab.There were 8 males and 6 females whose ages ranged from 50 to 82 years with an mean age of 67 years.There were 8 cases of adenocarcinoma,5 cases of squamous cell carcinoma,and 1 case with unknown NSCLC type.Most of the myocarditis(13 cases,92.8%)occurred within the first 3 cycles of using PD-1 inhibitors,of which the interval time between the last dose and the onset of myocarditis ranged from 1 to 19 days and the median(interquartile range)of 6(4,15)days.The most common clinical symptoms were dyspnea(7 cases),followed by myalgia(6 cases)and fatigue(5 cases).In addition to myocarditis,other immune-related adverse events included myositis(5 cases),myasthenia gravis(5 cases),hepatitis(5 cases),etc.Cardiac troponin I or T were detected in all 14 cases,and the values were higher than respective upper limit of reference.There were 11 cases with abnormal electrocardiogram,including non-specific ST-T changes(7 cases),complete right bundle branch block(5 cases),ventricular premature beats(3 cases)and ventricular tachycardia(3 cases).Among 13 cases with echocardiographic results,left ventricular ejection fraction(LVEF)was recorded in 6 cases,of which,only 2 cases with LVEF<50%and other 4 cases with LVEF of 51%~63%.

关 键 词：程序性细胞死亡蛋白-1抑制剂 心肌炎 肺癌 病例分析 

分 类 号：R734.2[医药卫生—肿瘤] R542.2[医药卫生—临床医学]