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Fulminant Myocarditis with Combination Immune Checkpoint Blockade.
Douglas B Johnson1, Justin M Balko1, Margaret L Compton1
1From the Departments of Medicine (D.B.J., J.M.B., M.H., I.P., M.R.A., T.L.B., J.R.B., D.A.S., E.J.P., M.A.P., D.M.R., J.A.S., J.J.M.), Cancer Biology (J.M.B., J.J.M.), Pathology, Microbiology, and Immunology (M.L.C., L.C.-O., R.D.H.), Biostatistics (Y.X.), Pharmacology (D.M.R.), and Biomedical Informatics (Y.X., D.M.R.), the Cardio-oncology Program (D.A.S., J.J.M.), the Breast Cancer Research Program (J.M.B.), and the Center for Quantitative Sciences (Y.X.), Vanderbilt University Medical Center, Nashville; the Department of Medicine (S.C.) and the Division of Neuroimmunology (S.C., I.J.K.), Beth Israel Deaconess Medical Center, the Departments of Medicine (B.A.O., C.E.S., J.G.S.) and Pathology (A.H.L.), Brigham and Women's Hospital, the Department of Genetics, Harvard Medical School (J.G., C.E.S., J.G.S.) - all in Boston; Howard Hughes Medical Institute, Chevy Chase, MD (C.E.S.); Bristol-Myers Squibb, New York (N.K., G.P., D.S.R., J.S.D.); Neon Therapeutics, Cambridge, MA (R.P.D.); and the Departments of Pathology (J.M.T., R.A.A.), Dermatology (J.M.T.), and Oncology (L.A.D.), Johns Hopkins University, Baltimore.
Fatal myocarditis is a rare, T-cell-driven adverse event in melanoma patients receiving combination immunotherapy (ipilimumab and nivolumab). This immune-related adverse event involves myositis, cardiac instability, and T-cell infiltration.
Area of Science:
- Oncology
- Immunology
- Cardiology
Background:
- Immune checkpoint inhibitors (ICIs) like ipilimumab and nivolumab have revolutionized cancer treatment.
- Combination immunotherapy can lead to severe immune-related adverse events (irAEs).
Observation:
- Two melanoma patients developed fatal myocarditis after ipilimumab and nivolumab treatment.
- Both patients exhibited myositis with rhabdomyolysis and cardiac electrical instability.
- Myocarditis showed significant T-cell and macrophage infiltration in cardiac tissue.
Findings:
- Clonal T-cell populations in the myocardium matched those found in tumors and skeletal muscle.
- Pharmacovigilance data indicates myocarditis occurs in 0.27% of patients on combination ipilimumab and nivolumab.
- These findings suggest a rare, T-cell-mediated drug reaction.
Implications:
- Highlights a rare but potentially fatal irAE of combination ICI therapy.
- Underscores the importance of monitoring cardiac function in patients receiving ICIs.
- Suggests a mechanism involving cross-reactivity of T-cells targeting tumor and cardiac antigens.
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