肿瘤免疫治疗相关的心脏毒性特点分析

Characteristics of cardiotoxicity related to cancer immunotherapy

目的探讨肿瘤患者接受免疫治疗后发生心脏毒性的临床特点及其预后情况。方法收集肿瘤免疫治疗相关心脏毒性患者的临床病历资料,回顾性分析肿瘤免疫治疗相关心脏毒性的临床特点,随访患者的生存情况,利用Kaplan-Meier法进行生存分析。结果35例免疫治疗相关心脏毒性患者中,男性多于女性,中位年龄62岁,既往合并心血管病史的比例高(54.3%)。接受PD-1单抗治疗24例,PD-L1单抗治疗3例,联合CTLA-4单抗或者抗体耦联药物8例。单纯免疫治疗19例,联合化疗8例,联合靶向治疗8例。从开始免疫治疗到发生心脏毒性的中位时间为40天,中位周期数为2周期。诊断为亚临床心肌损伤患者18例,有可能的心肌炎患者16例,可能性较大的心肌炎患者1例。18例(51.4%)患者合并其他免疫相关不良反应。28例患者接受糖皮质激素治疗。31例患者永久终止免疫治疗,4例患者后期重启免疫治疗。患者的中位生存期为24个月。结论肿瘤免疫治疗相关的心脏毒性发生时间较早,以亚临床心肌损伤和有可能的心肌炎为主,对患者的长期预后可能影响不大。

Objective To investigate the clinical characteristics and prognosis of cancer patients with cardiotoxicity after immunotherapy.Methods We collect the clinical records of patients with tumor immunotherapy related cardiotoxicity,retrospectively analyze their clinical characteristics.Then follow up the survival of those patients.The survival analysis is performed by Kaplan-Meier method.Results Among the 35 patients with immunotherapy related cardiotoxicity,men were more than women,the median age is 62 years old.The proportion of previous cardiovascular history is high(54.3%).24 cases were treated with PD-1 monoclonal antibody,3 cases with PD-L1 monoclonal antibody,and 8 cases combined with CTLA-4 monoclonal antibody or coupled-antibody drugs.There were 19 cases of simple immunotherapy,8 cases of combined chemotherapy and 8 cases of combined targeted therapy.The median time from the start of immunotherapy to cardiotoxicity is 40 days,and the median number of cycles was 2.18 cases are diagnosed as"subclinical myocardial injury",16 cases as"possible myocarditis",while one case is diagnosed as"probable myocarditis".18 patients(51.4%)were complicated with other immune related adverse reactions.28 patients were treated with glucocorticoids.31 patients permanently terminated immunotherapy,and 4 patients restarted immunotherapy later.The median survival is 24 months.Conclusions The cardiotoxicity related to tumor immunotherapy occurs at early stage,mainly as"possible myocarditis"and"subclinical myocardial injury".It has modest impact on the long-term prognosis of patients.