Immune-mediated adverse effects of immune checkpoint inhibitors are rather common, but neuromyopathic immune-related adverse events are very rare. In this report, we present a unique case of a patient with a complex neuromyopathic syndrome with axonal neuropathy and inflammatory myopathy after a single dose of pembrolizumab. An 82-year-old patient with a previously untreated stage IIIc melanoma developed ptosis in the left eye, generalized weakness, and neck and shoulder pain 15 days after pembrolizumab administration. He had left-sided ptosis and miosis, with a normal pupillary light reflex, horizontal diplopia, and voice hoarseness, along with weakness of the neck muscles and a hypokinetic right vocal cord at laryngoscopy. The laboratory evaluation was remarkable for the marked increase in the serum lactate dehydrogenase and creatine phosphokinase levels. Further evaluation revealed findings compatible with axonal neuropathy and inflammatory myopathy. The patient was treated with corticosteroids, immunoglobulin, and plasmapheresis, with a minor response; the patient eventually died. This case represents a newly described syndrome probably associated with pembrolizumab administration.

Immune checkpoint inhibitors (ICI) have altered the prognosis of patients with melanoma over the past few years, with immune-related adverse effects (irAEs) being the only factor limiting their use. Neurologic and cardiac irAEs are rare, but usually severe. We reviewed the files of patients with melanoma treated with ICIs in one center to retrieve data from patients with neurologic irAEs. Patients with a combination of neurologic and cardiac manifestations were further analyzed. We also reviewed the literature for similar syndromes. Five out of 482 (1.01%) patients developed a neurologic syndrome and we present three patients with a constellation of neurologic and cardiac irAEs. A 66-year-old woman and a 68-year-old man presented with a constellation of findings after being treated with ipilimumab and nivolumab, respectively, for melanoma in the adjuvant setting and were eventually diagnosed with myasthenia gravis with cardiac involvement. An 80-year-old woman developed diffuse asymmetric muscle weakness, bilateral ptosis and asymptomatic high serum troponin levels after adjuvant treatment with nivolumab and ipilimumab for a stage IIIB melanoma. After excluding ischemic heart disease, she was diagnosed with axonal polyradiculoneuropathy and myocarditis. Neurologic or cardiac irAEs in patients treated with ICIs are uncommon (<1%), but usually severe, with high rates of morbidity and fatality. The co-development of neurologic and cardiac irAEs is even more rare and can arise soon after exposure to ICIs and escalate rapidly. Since more and more patients are now treated with ICIs in the adjuvant setting, prompt identification and management are essential to avoid serious complications or death.