Immune checkpoint inhibitor-related myocarditis in patients with lung cancer

肺癌患者免疫检查点抑制剂相关性心肌炎

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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.

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