Late-onset immune checkpoint inhibitor-associated myocarditis: A systematic review and patient-level synthesis.
Priyanth Alaguraja, Eyad Mohammed Eldesouki, Saeed Kadri et al.
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In 30 seconds
This PRISMA 2020 systematic review and patient-level synthesis examined the timing, clinical features, management and outcomes of immune checkpoint inhibitor-associated myocarditis presenting at least 90 days after the first dose. Thirty studies contributed 30 cases to the primary analysis, with nine additional cases included only in sensitivity analysis. Median onset was 9.0 months (IQR 6.2-12.8); among patients with known treatment status, 8/21 (38.1%) presented after ICI discontinuation. The reported cases showed heterogeneous severity, including frequent arrhythmic or conduction complications and substantial mortality.
Key findings
- Median onset was 9.0 months (IQR 6.2-12.8), and 3/30 (10.0%) cases presented at ≥ 24 months.
- Among patients with known treatment status, 8/21 (38.1%) presented after ICI discontinuation.
- Major arrhythmic or conduction complications occurred in 10/19 (52.6%); left ventricular ejection fraction was < 50% in 18/26 (69.2%).
- Nine of 29 patients died (31.0%), including three myocarditis/cardiac deaths; 11/19 (57.9%) with ascertainable recovery achieved complete recovery.
Why it matters
The synthesis indicates that myocarditis associated with immune checkpoint inhibitors may present well beyond the period commonly considered early toxicity, including after treatment has stopped. The reported cases also include serious cardiac complications and deaths. Awareness of this timing and range of outcomes can inform clinical consideration of myocarditis in patients with relevant prior exposure and compatible presentations.
What to keep in mind
The evidence is a synthesis of published studies and cases, with only 30 cases meeting primary-analysis criteria; outcome denominators vary because data were not available for every patient.