Immune checkpoint inhibitor-associated myocarditis: a historical and comprehensive review

Abstract

The most fatal side effect associated with revolutionary immune checkpoint inhibitor (ICI) cancer therapies is myocarditis, a rare and devastating complication with a mortality rate approaching 40%. This review comprehensively examines the limited knowledge surrounding this recently recognized condition, emphasizing the absence of evidence-based therapeutic strategies, diagnostic modalities, and reliable biomarkers that hinder effective management. It explores advancements in preclinical models that are uncovering disease mechanisms and enabling the identification of therapeutic targets. These efforts have informed the design of early clinical trials aimed at reducing mortality. With the growing prevalence of ICI therapies in oncology, addressing critical gaps, such as long-term outcomes and risk stratification, has become increasingly urgent. By synthesizing current evidence, this work seeks to enhance understanding and guide the development of strategies to improve patient outcomes and ensure the continued safe use of ICIs in cancer care.

Keywords: cancer immunotherapy; immune checkpoint inhibitors; immune related adverse events; myocarditis.

Figure 1 –

clinical presentation of ICI myocarditis H&E-stained myocardium obtained from an endomyocardial biopsy of an ICI myocarditis patient demonstrating patchy intramyocardial lymphocytic infiltrates (left), CD8 immunohistochemistry staining of myocardium demonstrating presence of intramyocardial CD8 T lymphocytes (middle), ECG demonstrating complete AV block from a patient diagnosed with ICI myocarditis.