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肺癌患者中免疫检查点抑制剂相关的心肌炎

Immune checkpoint inhibitor-related myocarditis in patients with lung cancer.

作者信息

Cao Wenli, Han Sen, Zhang Panpan, Mi Lan, Wang Yang, Nie Jun, Dai Ling, Hu Weiheng, Zhang Jie, Chen Xiaoling, Ma Xiangjuan, Tian Guangming, Han Jindi, Wu Di, Long Jieran, Zhang Ziran, Hao Qianyun, Fang Jian, Wang Kai

机构信息

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Oncology II, Peking University Cancer Hospital & Institute, Haidian District, 52# Fucheng Road, Beijing, 100142, China.

Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Haidian District, 52# Fucheng Road, Beijing, 100142, China.

出版信息

BMC Cancer. 2025 Apr 14;25(1):685. doi: 10.1186/s12885-025-13997-1.

Abstract

BACKGROUND

The clinical characteristics of immune checkpoint inhibitors (ICIs)-related myocarditis in lung cancer remains uncertain. The purpose of this study was to evaluate the incidence, clinical characteristics, risk factors, and prognosis of myocarditis in lung cancer patients treated with ICIs. Therefore, this study would enhance the understanding of immune related myocarditis in lung cancer population.

METHODS

A total of 1004 patients were analyzed, among those who developed elevated serum creatine kinase isoenzyme, MB form (CK-MB) and/or high-sensitivity troponin I (hs-cTnI) with electrocardiographic or clinical symptoms after immunotherapy were enrolled in the myocarditis group. The same number of patients who had received immunotherapy but didn't develop myocarditis was randomly selected as the control group. Clinicopathologic features, risk factors, and prognostic factors were evaluated in this study.

RESULTS

66 patients (6.6%) developed ICIs-related myocarditis. In these patients, there were 60 case of possible myocarditis (90.9%), 5 probable myocarditis (7.6%), and 1 definite myocarditis (1.5%). The median time to the occurrence of myocarditis was 3.8 months. The median progression-free survival (PFS) for NSCLC and SCLC patients were 24.4 months and 13.0 months, while the median overall survival (OS) for NSCLC and SCLC patients were 43.3 months and 44.6 months. The grade of myocarditis (OR: 5.79; 95%CI: 1.14-29.41, P = 0.034), immunotherapy cycle (OR: 0.38; 95% CI: 0.16-0.92, P = 0.032), and combination of immune-related adverse events (irAEs) (OR: 3.63; 95% CI: 1.55-8.48, P = 0.003) were the influencing factors of PFS in NSCLC patients. In SCLC patients, the immunotherapy cycle was the influential factor for PFS (OR: 0.16; 95%CI: 0.04-0.61, P = 0.007) and OS (OS: 0.12; 95% CI: 0.03-0.48, P = 0.002). Anti-PD1 therapy (OR: 0.4, 95% CI: 0.13-0.97, P = 0.043) and age (OR: 0.36, 95% CI: 0.16-0.84, P = 0.018) might be the protective factors of myocarditis patients compared with the control group.

CONCLUSIONS

The presentations of ICIs-related myocarditis in lung cancer are mainly possible myocarditis and probable myocarditis, which have a mild impact on the prognosis. More cycles of ICI treatment accompany the longer the PFS and OS, as a protective factor. Anti-PD1 therapy and older age may be protective factors for ICI-related myocarditis.

摘要

背景

肺癌中免疫检查点抑制剂(ICI)相关心肌炎的临床特征仍不明确。本研究的目的是评估接受ICI治疗的肺癌患者中心肌炎的发生率、临床特征、危险因素和预后。因此,本研究将增进对肺癌人群中免疫相关心肌炎的了解。

方法

共分析1004例患者,其中免疫治疗后出现血清肌酸激酶同工酶MB型(CK-MB)升高和/或高敏肌钙蛋白I(hs-cTnI)升高且伴有心电图或临床症状的患者纳入心肌炎组。随机选择相同数量的接受免疫治疗但未发生心肌炎的患者作为对照组。本研究评估了临床病理特征、危险因素和预后因素。

结果

66例患者(6.6%)发生ICI相关心肌炎。在这些患者中,可能心肌炎60例(90.9%),很可能心肌炎5例(7.6%),确诊心肌炎1例(1.5%)。心肌炎发生的中位时间为3.8个月。非小细胞肺癌(NSCLC)和小细胞肺癌(SCLC)患者的中位无进展生存期(PFS)分别为24.4个月和13.0个月,而NSCLC和SCLC患者的中位总生存期(OS)分别为43.3个月和44.6个月。心肌炎分级(OR:5.79;95%CI:1.14-29.41,P = 0.034)、免疫治疗周期(OR:0.38;95%CI:0.16-0.92,P = 0.032)和免疫相关不良事件(irAE)的组合(OR:3.63;95%CI:1.55-8.48,P = 0.003)是NSCLC患者PFS的影响因素。在SCLC患者中,免疫治疗周期是PFS(OR:0.16;95%CI:0.04-0.61,P = 0.007)和OS(OR:0.12;95%CI:0.03-0.48,P = 0.002)的影响因素。与对照组相比,抗PD1治疗(OR:0.4,95%CI:0.13-0.97,P = 0.043)和年龄(OR:0.36,95%CI:0.16-0.84,P = 0.018)可能是心肌炎患者的保护因素。

结论

肺癌中ICI相关心肌炎的表现主要为可能心肌炎和很可能心肌炎,对预后影响较小。作为一个保护因素,ICI治疗周期越多,PFS和OS越长。抗PD1治疗和年龄较大可能是ICI相关心肌炎的保护因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4f0/11995475/b26045aac22a/12885_2025_13997_Fig1_HTML.jpg

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