Immune checkpoint inhibitors-induced neuromuscular toxicity: From pathogenesis to treatment

Dimitri Psimaras1,2,3, Roser Velasco4,5,6, Cristina Birzu1,2,3

  • 1AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, Service de Neurologie Mazarin, Paris, France.

Immune checkpoint inhibitors (ICIs) are increasingly used and are becoming the standard of care in the treatment of various tumor types. Despite the favorable results in terms of oncological outcomes, these treatments have been associated with a variety of immune-related adverse events (irAEs). Neurological irAEs are rare but potentially severe. Neuromuscular disorders represent the most common neurological irAEs following anti-PD-1, anti-PD-L1, and anti-CTLA-4 treatment, and include myositis, myasthenia gravis, and demyelinating polyradiculoneuropathy. Instrumental findings may differ from typical neuromuscular disorders occurring outside ICIs treatment. Despite initial severity, neurological irAEs often respond to immune-modulating therapies. Prompt irAEs diagnosis, ICIs discontinuation, and early treatment with corticosteroids, together with patient education and a multi-disciplinary approach, are important for optimizing clinical outcomes. Intravenous immunoglobulin, plasma exchange, and other immune-modulating treatments should be considered in more severe cases. Consideration of re-challenging with the same immunotherapy drug may be given in some cases, based on clinical picture and initial severity of irAEs.

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