Severe Myositis, Myocarditis, and MyastheniaGravis with Elevated Anti-Striated Muscle Antibody followingSingle Dose of Ipilimumab-Nivolumab Therapy in a Patient withMetastatic Melanoma

Immune checkpoint inhibitors targeting programmed cell death protein 1 and cytotoxic T-lymphocyte associated protein 4 haveimproved survival in patients with metastatic melanoma, especially in combination (i.e., ipilimumab-nivolumab). Postmarketingsurveillance has identified rare but at times life-threatening adverse effects associated with these agents in combination and asmonotherapy, which include myocarditis, myositis, myasthenia gravis (MG), and hepatotoxicity. Further evaluation of immunecheckpoint therapy-induced MG identified the rapid clinical progression, prolonged treatment/supportive therapy course, andhigher frequency of myasthenic crisis in these patients versus those with idiopathic MG. More rapid incorporation of aggressivetreatment options (i.e., intravenous immunoglobulin, plasmapheresis) may be necessary in these cases. Anti-striational antibodiesare often detected in individuals with myasthenia gravis and concurrent myositis and myocarditis. A high-index of suspicion isnecessary to assist with rapid treatment initiation as these patients can rapidly deteriorate into respiratory compromise. A caseof a 78-year-old woman with metastatic melanoma status after combination therapy with ipilimumab-nivolumab that developedtransaminitis, myositis, myocarditis, and myasthenia gravis (with positive anti-striational antibodies) five days after the first cycle, ispresented. Despite high dose intravenous methylprednisolone and intravenous immunoglobulin treatment, she ultimately enteredhospice care eight days after hospital admission, 36 days after her first cycle.