Inflammatory Myopathy and Axonal Neuropathy in a Patient With Melanoma Following Pembrolizumab Treatment

Abstract

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.

Severe Neurological Toxicity of Immune Checkpoint Inhibitors: Growing Spectrum

“…Although short courses of prednisone started after ICI infusion do not appear to reverse the antitumor effect of the ICI, the influence of immunosuppression for irAEs or longer courses of steroids on cancer outcomes remains unknown . Clinical phenotypes, including encephalitis, neuropathies, myasthenia gravis (MG), and myositis, are described in small case series or case reports . However, these reports have generally been limited to single malignancies (melanoma) and/or ICI class (anti–PD‐1 antibodies) .…”

Pembrolizumab-Induced Isolated Cranial Neuropathy: A Rare Case Report and Review of Literature

“…Conversely, in other cases of isolated pembrolizumab-derived cranial nerve disorders, patients have been usually reported to have mononeuropathies (mostly facial palsies) or involvement of few cranial nerves ( 18 ). Finally, IVIg therapy (not associated to steroids) dramatically impacted the clinical course of the disease, with an improvement of both symptoms and neurophysiological tests since the first cycle: in literature, only two patients were treated with IVIg alone ( 9 , 10 ), while the most common strategies were a combination of steroids, plasma exchange, and/or IVIg.…”

“…We identified 24 cases of pembrolizumab-induced neuropathies and/or radiculopathies, mostly reported in small series of single or few patients (Table 2) (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Melanoma was the primary tumor in 20 cases, whereas only three patients had lung adenocarcinoma (6,7,16).…”

Therapeutic plasma exchange in the management of immune checkpoint inhibitor‐associated immune‐related adverse effects: A review

“…Other neurologic irAEs for which TPE has been used include enteric plexus neuropathy, 74 inflammatory and axonal neuropathy, 75 CNS demyelinating disease, 76 demyelinating polyneuropathy, 77 acute motor polyradiculopathy, 78 and sensorineural hearing loss 79 . In these studies, the number of TPE procedures ranged from 2 to 7.…”