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Immune Checkpoint Inhibitors in Patients with Pre-existing Neurologic Autoimmune Disorders

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Abstract

Purpose of Review

The use of immune checkpoint inhibitors (ICIs) for oncologic indications is associated with immune-related adverse events (irAEs). Patients with pre-existing autoimmune diseases are at increased risk of irAEs and have largely been excluded from clinical trials of ICIs. Therefore, there is limited data on the safety of safety of ICIs in patients with pre-existing neurologic autoimmune diseases (nAIDs) such as myasthenia gravis and multiple sclerosis. This review aims to synthesize the literature on the post-marketing experience with ICI in patients with pre-existing nAID and to discuss possible strategies for mitigating the risk of post-ICI nAID relapses.

Recent Findings

Patients with pre-existing myasthenia gravis (MG), myositis, and paraneoplastic encephalitis appear highly susceptible to neurologic relapses of their underlying neurologic disorder following ICI initiation; these relapses can cause considerable morbidity and mortality. In patients with multiple sclerosis (MS), the risk and severity of MS relapses following ICI appears to be relatively lower compared to MG. Preliminary evidence suggests that older MS patients with no recent focal neuroinflammatory activity may be safely treated with ICI. Among the several case reports of ICI in patients with a history of Guillain–Barre syndrome (GBS), neurologic worsening was only recorded in one patient who was in the acute phase of GBS at the time of ICI start.

Summary

Initiating an ICI in a patient with pre-existing nAID involves a complex risk-benefit discussion between the patient, their oncologist, and neurologist. Relevant issues to consider before ICI include the choice of disease-modifying therapy for nAID (if any) and strategies for promptly identifying and managing nAID relapses should they occur. Currently, the literature consists mainly of case reports and case series, subject to publication bias. Prospective studies of ICI in patients with nAID are needed to improve the level of evidence.

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Acknowledgements

We would like to thank Drs. Omar Hasan Ali, Massimo Filippi, Lisa Ann Gerdes, and Thomas Scott for providing us with additional data regarding their published cases.

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  1. Raissa Aoun and Daniel Gratch contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, NYU Grossman School of Medicine, 550 1st Ave, New York, NY, 10016, USA

    Raissa Aoun

  2. Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, 5 East 98th St, New York, NY, 10029, USA

    Daniel Gratch

  3. Department of Oncology, NYU Grossman School of Medicine, 550 1st Ave, New York, NY, 10016, USA

    David Kaminetzky

  4. NYU Multiple Sclerosis Comprehensive Care Center, Department of Neurology, NYU Grossman School of Medicine, 240 East 38th St, New York, NY, 10016, USA

    Ilya Kister

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Raissa Aoun, Daniel Gratch, and David Kaminetzky each declare no potential conflicts of interest.

Ilya Kister served on advisory boards for Biogen, Genentech, Horizon and Alexion Pharmaceuticals, and received research support for investigator-initiated grants from Genentech, Sanofi Genzyme, Biogen, EMD Serono, National MS Society, and Guthy Jackson Charitable Foundation. He received royalties from Walters-Kluwer for “Top 100 Diagnosis in Neurology.”

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Aoun, R., Gratch, D., Kaminetzky, D. et al. Immune Checkpoint Inhibitors in Patients with Pre-existing Neurologic Autoimmune Disorders. Curr Neurol Neurosci Rep 23, 735–750 (2023). https://doi.org/10.1007/s11910-023-01306-x

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