Abstract

Immune checkpoint inhibitor (ICI)-associated myocarditis is a rare but severe complication for patients treated with immunotherapy. This study aims to explore the predictive significance of patients' clinical features and examination results for the severity of ICI-associated myocarditis. Data from a real-world cohort of 81 cancer patients who developed ICI-associated myocarditis after immunotherapy were retrospectively analyzed. The development of myocarditis of Common Terminology Criteria for Adverse Events (CTCAE) grades 3-5 and/or the major adverse cardiovascular event (MACE) was set as endpoints. Logistic regression was used to evaluate the predictive value of each factor. CTCAE grades 3-5 and MACE developed in 43/81 (53.1%) and 28/81 (34.6%) cases, respectively. The likelihood of CTCAE grades 3-5 and MACE increased with the accumulation of organs affected by the ICI-associated adverse events and initial clinical symptoms. Concurrent systematic therapies during ICI treatment did not raise the risk of myocarditis severity, while prior chemotherapy did. Besides classical serum cardiac markers, a higher neutrophil ratio was also related to poorer cardiac outcomes, whereas higher lymphocyte and monocyte ratios were predictors of favorable cardiac outcomes. The CD4+ T cell ratio and CD4/CD8 ratio were negatively related to CTCAE grades 3-5. Several cardiovascular magnetic resonance parameters were associated with myocarditis severity, whereas the predictive value of echocardiography and electrocardiogram was weak. This study comprehensively evaluated the prognostic value of patients' clinical characteristics and examination results and identified several predictors of severe ICI-associated myocarditis, which will facilitate early detection of severe ICI-associated myocarditis in patients receiving immunotherapy.

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