摘要
目的 探讨肺癌患者接受免疫检查点抑制剂(ICIs)治疗后发生心脏毒性的临床特点及预后情况.方法 回顾性分析2016年1月至2023年12月在北京大学肿瘤医院胸部肿瘤内二科接受免疫治疗的1 004例肺癌患者的病例资料,以免疫治疗后血清肌酸激酶同工酶(CK-MB)和(或)高敏肌钙蛋白I(hs-cTnI)升高(高于参考值上限)为主要标准,筛选出ICIs相关心脏毒性的患者,分析其临床特点及预后情况.结果 本组患者中65例(6.5％)出现不同程度的心脏毒性,其中男性49例、女性16例,中位年龄65岁(47～85岁).病理类型:非小细胞肺癌(NSCLC)42例,小细胞肺癌(SCLC)23例.免疫治疗:PD-1单抗治疗44例(67.7％),PD-L1单抗治疗11例(16.9％),联合其他ICIs治疗10例(15.4％).单纯免疫治疗10例(15.4％),免疫治疗联合其他抗肿瘤治疗55例(84.6％).发生时间:从开始免疫治疗到出现心脏毒性的中位时间为110 d(1～759 d),中位周期数为3周期.临床表现:15例(23.1％)患者发病时有临床症状,41例(63.1％)伴随心电图改变.临床诊断:亚临床心肌损伤59例(90.8％),有可能的心肌炎5例(7.7％),明确的心肌炎1例(1.5％).治疗方案:16例(24.6％)患者接受糖皮质激素治疗;17例(26.2％)患者永久终止免疫治疗,41例(63.1％)重启免疫治疗,7例(10.8％)后续治疗情况不详.预后情况:NSCLC患者的中位无进展生存期(PFS)为 732 d(95％CI:378～1 085 d),SCLC 患者的中位 PFS 为 391 d(95％CI:0～900 d).结论 肺癌患者出现免疫治疗相关的心脏毒性在临床并不罕见,以接受PD-1单抗治疗和与其他抗肿瘤治疗联合时更易发生,且发生时间较早,以亚临床心肌损伤和有可能的心肌炎为主要类型,不过对患者的总体预后影响不大.
Abstract
Objective To investigate the clinical characteristics and prognosis of cardiotoxicity in lung cancer patients treated with immune checkpoint inhibitors(ICIs).Methods The clinical records of lung cancer patients who received immunotherapy in the second Department of Thoracic Oncology,Beijing Cancer Hospital from January 2016 to December 2023 were selected.The main inclusion criteria were higher than normal value of serum creatine kinase isoenzyme MB(CK-MB)and/or high-sensitivity cardiac troponin I(hs-cTnI)after immunotherapy.Their clinical characteristics and prognosis were analyzed.Results Of 1 004 patients,65(6.5％)developed cardiotoxicity of varying degrees.There were 49 male patients and 16 female patients,and the median age was 65 years old.Among them,42 cases were non-small cell lung cancer(NSCLC)and 23 cases were small cell lung cancer(SCLC).There were 44 patients(67.7％)under treatment with PD-1(programmed cell death 1)monoclonal antibody and 11 patients(16.9％)with PD-L1(programmed cell death ligand 1)monoclonal antibody.10 cases(15.4％)were treated with other ICIs.Ten cases(15.4％)received immunotherapy alone and 55 cases(84.6％)received immunotherapy combined with other anti-tumor therapy.Fifteen patients(23.1％)had clinical symptoms.Electrocardiographic changes were found in 41 cases(63.1％).The median time from initiation of immunotherapy to the onset of cardiotoxicity was 110 days and the median number of cycles was 3.There were 59 patients with subclinical myocardial injury,5 with probable myocarditis and 1 with definite myocarditis.Sixteen patients(24.6％)received glucocorticoid therapy.Seventeen patients(26.2％)permanently terminated immunotherapy,41 patients(63.1％)restarted immunotherapy,and 7 patients(10.8％)had no follow-up status.The median progression free survival(PFS)of patients with NSCLC was 732 days(95％CI:378-1 085 days)and the median PFS of patients with SCLC was 391 days(95％CI:0-900 days).Conclusions Immunotherapy-related cardiotoxicity in lung cancer is not rare,and it is more likely to occur when receiving PD-1 monoclonal antibody immunotherapy or in combination with other anti-tumor therapies.It usually occurs in the early stage of immunotherapy.ICIs-related cardiotoxicities of lung cancer are mainly subclinical myocardial injury and possible myocarditis,which has mild effect on the overall prognosis of patients.
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