Cardiac antigen identified as mechanism for heart complication with immunotherapy-related myocarditis nature nejm
Myocarditis was rarely reported in early clinical trials with anti–CTLA-4 and anti–PD-1 agents , which resulted in one death in a patient receiving adjuvant treatment with ipilimumab at a dose of 10 mg per kilogram.Our review of a large safety database suggests that myocarditis is more frequent and severe with the combination of ipilimumab and nivolumab than with nivolumab monotherapy, but the condition remains rare with both regimens, occurring in less than 1% of patients.
Clinicians should be vigilant for immune-mediated myocarditis, particularly because of its early onset, nonspecific symptomatology, and fulminant progression. There are no known data regarding what monitoring strategy may be of value; in our practice, we are performing baseline ECG and weekly testing of troponin levels during weeks 1 to 3 for patients receiving combination immunotherapy.
We sought to characterize these aberrant immune responses mechanistically. Notably, striated muscle and tumor were the only affected tissues. Robust T-cell infiltration, activation, and clonal expansion were observed across tissue types, with indications of shared high-frequency T-cell receptors. There are several possible mechanisms for the observed toxic effects.
The development of myocarditis from immune checkpoint inhibition does have biologic plausibility. In studies in mice, PD-1 plays a role in myocardial immune responses and protects against inflammation and myocyte damage in models of T-cell–mediated myocarditis.
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