A systematic review of immune checkpoint inhibitor-related neurological adverse events and association with anti-neuronal autoantibodies

ABSTRACT

Introduction: Immune checkpoint inhibitors (ICI) therapy has led to a paradigm shift in cancer drug development and in the clinical evaluation of approaches to combination cancer treatment. Dysregulation of the immune system by ICI therapy may also elicit autoimmune phenomena and consequently manifest clinically as immune-related adverse events (irAEs) including neurological irAEs. Areas Covered: The purpose of this review is to explore the role of autoantibodies in the diagnosis and prediction of neurological irAEs and to evaluate their pathogenicity. We searched Pubmed and Embase for neurological irAEs and associated autoantibodies and found 28 patients with central and peripheral neurological irAEs. Of these patients, up to 40% had encephalitis, 34.4% with myasthenia gravis and 22% of patients with peripheral neuropathy and Guillain-Barre Syndrome had autoantibodies. Expert Opinion: Overall, our survey suggested a causal relationship between neurological irAEs and autoantibodies. Detection of autoantibodies may help to diagnose neurological irAEs and inform their clinical management.

KEYWORDS:

• Autoantibodies
• neurological immune related adverse events
• immune checkpoint inhibitors
• encephalitis
• neuromuscular disorders
• peripheral neuropathy
• radiculopathy
• myasthenia gravis
• guillain-Barre syndrome

Article highlights

• Immunotherapy using immune checkpoint inhibitors (ICIs) is now indicated for a wide range of cancer diagnoses.

• ICI therapy has significantly increased tumor response rates and produced durable responses, which are often associated with prolonged survival but at the cost of immune related adverse events (irAEs).

• In this review, we describe the incidence of neurological irAEs with ICI therapy and describe autoantibodies that have been associated with neurological irAEs and their relevance to diagnosis and pathogenicity.

• Autoantibodies were found in up to 40% of cancer patients who had peripheral and central neurological irAEs in association with ICI therapy.

• These autoantibodies, when present, can aid the diagnosis of neurological irAEs and may be used to predict them.

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Declaration of interest

MP Brown receives honoraria from BMS Australia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One of the reviewers declares no direct conflict of interest with respect to this particular paper, but they have received honoraria from Grifols, CSL, Lupin and Akcea for speakers’ fees and advisory roles. Additional peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Table

ANNA-1, antineuronal anti-nuclear antibody 1; ANNA-2, anti-neuronal nuclear antibodies 2; Anti- GAD, Anti-glutamic acid decarboxylase antibodies; Anti-NMDAR antibodies, Anti N methyl D-aspartate antibodies; Anti-VGCC, Anti-voltage-gated calcium channel; Anti- acetylcholine receptor antibodies.

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Additional information

Funding

This paper was not funded.