Fatal myocarditis and rhabdomyositis in a patient with stage IV melanoma treated with combined ipilimumab and nivolumab.

ABSTRACT

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.