Neurological complications of immune checkpoint inhibitors: what happens when you 'take the brakes off' the immune system.

Authors

Marinos Dalakas, Thomas Jefferson University; University of Athens Medical SchoolFollow

Document Type

Article

Publication Date

9-14-2018

Comments

This article has been peer reviewed. It is the author’s final published version in Therapeutic Advances in Neurological Disorders, Volume 11, September 2018.

The published version is available at https://doi.org/10.1177/1756286418799864. Copyright © Dalakas

Abstract

Patients with advanced malignancies treated with immune checkpoint inhibitors are at increased risk for developing immune-related neurological complications. It is a phenomenon of immunological twist when immunotherapy against co-stimulatory molecules activates previously normal T cells to kill tumor cells but, in so doing, the T cells become unrestrained, triggering other autoimmune diseases for which conventional immunotherapy is needed. The most common autoimmune neurological diseases, usually occurring within 2-12 weeks after immune checkpoint inhibitor initiation, include: inflammatory myopathies, myasthenia gravis, acute and chronic demyelinating polyradiculoneuropathies, vasculitic neuropathies, isolated cranial neuropathies, aseptic meningitis, autoimmune encephalitis, multiple sclerosis and hypophysitis. The neurological events can evolve rapidly, necessitating the need for vigilance at all stages of treatment, even after completion, because early immunotherapeutic interventions are effective. The review addresses these complications and the applied therapies, discusses immune pathomechanisms including triggering preexisting autoimmunity, highlights the distinction between paraneoplastic and autoimmune etiologies, and identifies uncertainties regarding risk factors, use of immune checkpoint inhibitors in patients with known immune diseases or restarting therapy after a neurological event. Although the autoimmune neurological complications are not very common, their incidence will likely increase as the use of immune checkpoint inhibitors in metastatic cancer is growing rapidly.

Recommended Citation

Dalakas, Marinos, "Neurological complications of immune checkpoint inhibitors: what happens when you 'take the brakes off' the immune system." (2018). Department of Neurology Faculty Papers. Paper 169.
https://jdc.jefferson.edu/neurologyfp/169

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

PubMed ID

30245744

Language

English