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How to diagnose and manage neurological toxicities of immune checkpoint inhibitors: an update

Journal of Neurology volume 269, pages 1701–1714 (2022)Cite this article

Abstract

As the use of cancer immunotherapy with immune checkpoint inhibitors (ICIs) is expanding rapidly for the treatment of many tumor types, it is crucial that both neurologists and oncologists become familiar with the diagnosis and treatment of neurological immune-related adverse events (n-irAEs). These are rare complications, developing in their severe forms in only 1–3% of the patients, but are highly relevant due to their mortality and morbidity burden. The diagnosis of n-irAEs is—however—challenging, as many alternative diagnoses need to be considered in the complex scenario of a patient with advanced cancer developing neurological problems. A tailored diagnostic approach is advisable according to the presentation, clinical history, and known specificities of n-irAEs. Several patterns characterized by distinct clinical, immunological, and prognostic characteristics are beginning to emerge. For example, myasthenia gravis is more likely to develop after anti-programmed cell death protein 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1) treatment, while meningitis appears more frequently after anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) therapy. Also, peripheral neuropathy and Guillain–Barré syndrome seem to be more common in patients with an underlying melanoma. Central nervous system disorders (CNS) are less frequent and are more often associated with lung cancer, and some of them (especially those with limbic encephalitis and positive onconeural antibodies) have a poor prognosis. Herein, we provide an update of the recent advances in the diagnosis and treatment of neurological toxicities related to ICI use, focusing on the exclusion of alternative diagnoses, diagnostic specificities, and treatment of n-irAEs.

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Data access, responsibility, and analysis

The Corresponding Author had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Funding

This study is supported by FRM (Fondation pour la recherche médicale, DQ20170336751) and has been developed within the BETPSY project, which is supported by a public grant overseen by the French National Research Agency (ANR), as part of the second “Investissements d´Avenir” program (reference ANR-18-RHUS-0012).

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Authors and Affiliations

  1. French Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, Lyon, France

    Alberto Vogrig, Sergio Muñiz-Castrillo, Antonio Farina, Jérôme Honnorat & Bastien Joubert

  2. Synatac Team, NeuroMyoGene Institute, INSERM U1217/CNRS UMR5310, Lyon, France

    Alberto Vogrig, Sergio Muñiz-Castrillo, Antonio Farina, Jérôme Honnorat & Bastien Joubert

  3. University Claude Bernard Lyon 1, Université de Lyon, Lyon, France

    Alberto Vogrig, Sergio Muñiz-Castrillo, Antonio Farina, Jérôme Honnorat & Bastien Joubert

  4. Centre de Référence National Pour les Syndromes Neurologiques Paranéoplasiques, Hôpital Neurologique, 59 Boulevard Pinel, 69677, Bron Cedex, France

    Bastien Joubert

Authors
  1. Alberto Vogrig
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  2. Sergio Muñiz-Castrillo
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  4. Jérôme Honnorat
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Contributions

Study concept and design: AV, JH. Acquisition of data: AV, SMC, AF, JH, BJ. Analysis and interpretation of data: AV, SMC, AF, JH, BJ. Drafting of the manuscript: AV, SMC, BJ. Critical revision of the manuscript for important intellectual content: AV, SMC, AF, JH, BJ. Study supervision: JH. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Bastien Joubert.

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Conflicts of interest

Dr. Vogrig reports receiving a fellowship grant from the European Academy of Neurology (EAN). No other disclosures were reported.

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Vogrig, A., Muñiz-Castrillo, S., Farina, A. et al. How to diagnose and manage neurological toxicities of immune checkpoint inhibitors: an update. J Neurol 269, 1701–1714 (2022). https://doi.org/10.1007/s00415-021-10870-6

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  • DOI: https://doi.org/10.1007/s00415-021-10870-6

Keywords

  • Neurologic adverse events
  • Immune checkpoint inhibitors
  • Neurological complications
  • Encephalitis
  • Myositis