Fulminant Myocarditis with Combination Immune Checkpoint Blockade

Summ a r yImmune checkpoint inhibitors have improved clinical outcomes associated with numerous cancers, but high-grade, immune-related adverse events can occur, particularly with combination immunotherapy.We report the cases of two patients with melanoma in whom fatal myocarditis developed after treatment with ipilimumab and nivolumab.In both patients, there was development of myositis with rhabdomyolysis, early progressive and refractory cardiac electrical instability, and myocarditis with a robust presence of T-cell and macrophage infiltrates.Selective clonal T-cell populations infiltrating the myocardium were identical to those present in tumors and skeletal muscle.Pharmacovigilance studies show that myocarditis occurred in 0.27% of patients treated with a combination of ipilimumab and nivolumab, which suggests that our patients were having a rare, potentially fatal, T-cell-driven drug reaction.(Funded by Vanderbilt-Ingram Cancer Center Ambassadors and others.)I mmune checkpoint inhibitors have transformed the treatment of several cancers by releasing restrained antitumor immune responses. 13][4][5] Other adverse events associated with these agents include dermatitis, endocrinopathies, colitis, hepatitis, and pneumonitis, which are all thought to arise from aberrant activation of autoreactive T cells. 6,7These toxic effects are more frequent and severe when ipilimumab and nivolumab are used in combination. 4Here, we report two cases of lethal myocarditis accompanied by myositis in patients treated with a combination of nivolumab and ipilimumab.