Concomitant myasthenia gravis, myositis, myocarditis and polyneuropathy, induced by immune-checkpoint inhibitors: A life–threatening continuum of neuromuscular and cardiac toxicity

Abstract

Immune-checkpoint inhibitors (ICIs) show a unique spectrum of immune-related adverse events (irAEs), even severe (grade 3–4) [1–3]. Herein we report two cases: a 72-year-old female and a 71-year-old male with renal cancer, who had a similar clinical presentation after the first cycle of nivolumab i.e. dropped head and limb weakness, progressing to inability to walk. Also the first neurophysiological investigation revealed quite a similar pattern, i.e. sensori-motor symmetrical polyneuropathy, with axonal and demyelinating features. Furthermore, a decremental response was detected at the repetitive 3 Hz stimulation. The concentric needle electrode revealed a myopathic pattern at interference; spontaneous activity appeared two weeks later. Intravenous immunoglobulins and steroids were administered. Despite a second immunoglobulin cycle and intravenous steroid bolus, the male patient died. He had a more severe hyperCKemia earlier at laboratory tests, in line with a more severe necrotizing myopathy. The reported cases extend and confirm previous evidence of a broad clinical spectrum of autoimmune-mediated, life-threatening, neuromuscular and cardiac toxicity of ICIs. An early electromyographic investigation should be performed in case of neuromuscular symptoms in ICI-treated. Moreover, an Italian registry of neuromuscular side effects of ICI-treated patients would be welcome, in order to identify individual risk profiles.