Inflammatory Cell Profiles in Early- and Late-Manifestation Immune Checkpoint Inhibitor Myocarditis

Area of Science:

• Cardiology
• Immunology
• Oncology

Background:

• Immune checkpoint inhibitors (ICIs) can cause myocarditis, typically within 90 days of treatment.
• Delayed myocarditis after ICI discontinuation is also observed, but its characteristics are not well understood.

Purpose of the Study:

• To compare the clinical features and myocardial histopathology of early- (<90 days) versus late- (≥90 days) manifestation ICI myocarditis.

Main Methods:

• Retrospective national cohort study of 35 patients undergoing endomyocardial biopsy for ICI myocarditis.
• Analysis of biopsy samples for inflammatory cell infiltration and myocardial inflammation severity.

Main Results:

• Late-manifestation ICI myocarditis (n=9) exhibited significantly less severe myocardial inflammation, including lower CD3+, CD8+ T cells, and CD68+ macrophages compared to early-manifestation cases (n=26).
• Early-manifestation cases had higher cardiac biomarkers and older age, with 2 deaths from myocarditis.
• Late-manifestation cases had higher cancer-related mortality (3 vs 2).

Conclusions:

• Late-manifestation ICI myocarditis may represent a distinct or attenuated inflammatory process.
• Despite milder inflammation, increased cancer mortality suggests careful consideration for ICI reinitiation in select late-manifestation patients.