Fatal Myocarditis and Rhabdomyositis in a Patient with Stage Iv Melanoma Treated with Combined Ipilimumab and Nivolumab

Combination immune checkpoint blockade with concurrent administration of the anti-CTLA4 antibody ipilimumab and the anti–PD-1 antibody nivolumab has demonstrated impressive responses in patients with advanced melanoma and other diseases. That combination has also been associated with increased toxicity, including rare immune-related adverse events. Here we describe a case of fatal steroid-refractory myocarditis and panmyositis associated with the use of this combination in a patient with metastatic melanoma. Correlative studies indicated increased levels of serum interleukin 6 in this patient at the onset of toxicity, suggesting a possible role for anti–interleukin 6 receptor antibodies in the treatment of subsequent cases of this rare, but fatal, toxicity.