ICI Myocarditis: Does Timing Define the Disease? | JACC Baran

Is immune checkpoint inhibitor (ICI)-associated myocarditis the same disease when it occurs early versus months after starting cancer therapy? Host Mitsuaki Sawano, MD, and co-host Shun Kohsaka, MD, welcome Kazuaki Maruyama, MD (Mie University), Shiro Nakamori, MD (Mie University), and Yuichi Tamura, MD (International University of Health and Welfare) to discuss their recent JACC: CardioOncology study examining inflammatory cell profiles in early- and late-manifestation ICI myocarditis. Using endomyocardial biopsy specimens from 35 patients across 11 Japanese centers, the investigators found substantially greater T-cell and macrophage infiltration in early cases, while late-manifestation cases showed less myocardial inflammation despite similar fibrosis and LVEF. We discuss whether timing may identify different inflammatory phenotypes, why clinical severity does not necessarily reflect the degree of myocardial inflammation, and the difficult clinical question of whether ICI therapy should always be permanently discontinued after suspected myocarditis. Finally, we explore how Japan’s unique experience with myocardial biopsy helped uncover these differences and whether carefully selected patients with late, milder presentations might eventually be considered for ICI rechallenge, while recognizing the hypothesis-generating nature of these findings.