Immune checkpoint Inhibitor-Related Myocarditis: A Comprehensive Analysis of Clinical Manifestations and Prognostic Factors.

Abstract

Background: Immune checkpoint inhibitors-related myocarditis (ICI-myocarditis) is a rare but potentially lethal complication of cancer immunotherapy. Extensive information concerning risk factors and outcomes is still insufficient.

Methods: This multi-center retrospective study enrolled 161 patients diagnosed with biopsy-proven or clinically diagnosed ICI-myocarditis. We performed thorough studies of clinical characteristics and management approaches. Time-to-event analyses, encompassing landmark analysis and competing risk models, were employed to identify early mortality predictors and evaluate long-term prognosis in survivors.

Results: ICI-myocarditis typically generally manifested early (median 4 weeks following ICI initiation), with mortality primarily occurring within 60 days. Significantly elevated cardiac troponin I (cTnI ≥ 50 times the upper reference limit) and reduced left ventricular ejection fraction (LVEF < 50%) were strong predictors of shortened survival. Landmark analyses revealed these factors influenced early but not long-term mortality beyond 60 days. Patients with concomitant myositis exhibited more fulminant presentations and higher early mortality, though long-term outcomes were comparable to those of isolated myocarditis. Multivariable analysis identified four independent predictors of cardiotoxicity-related death: initial LVEF < 50%, alanine aminotransferase (ALT), creatine kinase-MB (CKMB) and concomitant ICI-myositis.

Conclusions: Our study identifies multiple key predictors of early mortality in ICI-myocarditis. These results underscore the significance of early detection and vigorous intervention, particularly in patients with extreme troponin elevation or overlapping myositis. Despite higher short-term mortality in high-risk patients, long-term prognosis among survivors appears comparable.