Fulminant Myocarditis with Combination Immune Checkpoint Blockade

Fatal autoimmune myocarditis with rhabdomyolysis and refractory arrhythmias developed in two patients treated with a combination of anti–CTLA-4 and anti–PD-1 blockers. On histologic examination, a myocardial infiltrate suggested acute cardiac allograft rejection. Immune checkpoint inhibitors have transformed the treatment of several cancers by releasing restrained antitumor immune responses. 1 Ipilimumab, an anti–cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) antibody, and nivolumab, an anti–programmed death-1 (PD-1) antibody, have individually improved survival in patients with melanoma, and early results suggest that their combination further enhances antitumor activity and survival. 2 – 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 , 7 These toxic effects are more frequent and severe when ipilimumab and nivolumab are used in combination. 4 Here, we report . . .