Neurologic autoimmunity and immune checkpoint inhibitors: Autoantibody profiles and outcomes

Elia Sechi, Svetomir N. Markovic, Andrew McKeon, Divyanshu Dubey, Teerin Liewluck, Vanda A. Lennon, A. Sebastian Lopez-Chiriboga, Christopher J. Klein, Michelle Mauermann, Sean J. Pittock, Eoin P. Flanagan, Anastasia Zekeridou

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

OBJECTIVE: To describe neural autoantibody profiles and outcomes in patients with neurologic autoimmunity associated with immune checkpoint inhibitor (ICI) cancer immunotherapy. METHODS: In this retrospective descriptive study, 63 patients with ICI-related neurologic autoimmunity were included: 39 seen at the Mayo Clinic Neurology Department (clinical cohort) and 24 whose serum/CSF was referred to the Mayo Clinic Neuroimmunology Laboratory for autoantibody testing. Serum/CSF samples were tested for neural-specific autoantibodies. Predictors of unfavorable outcome (residual adverse event severity grade ≥3) were explored (logistic regression). RESULTS: Median age at neurologic symptom onset was 65 years (range 31-86); 40% were female. Neurologic manifestations were CNS-restricted (n = 26), neuromuscular (n = 30), combined (n = 5), or isolated retinopathy (n = 2). Neural-specific autoantibodies were common in patients with CNS involvement (7/13 [54%] in the unbiased clinical cohort) and included known or unidentified neural-restricted specificities. Only 11/31 patients with CNS manifestations had neuroendocrine malignancies typically associated with paraneoplastic autoimmunity. Small-cell lung cancer (SCLC)-predictive antibodies were seen in 3 patients with non-neuroendocrine tumors (neuronal intermediate filament immunoglobulin G [IgG] and antineuronal nuclear antibody 1 with melanoma; amphiphysin IgG with non-SCLC). A median of 10 months from onset (range, 0.5-46), 14/39 in the clinical cohort (36%) had unfavorable outcomes; their characteristics were age ≥70 years, female, CNS involvement, lung cancer, higher initial severity grade, and lack of systemic autoimmunity. By multivariate analysis, only age remained independently associated with poor outcome (p = 0.01). Four of 5 patients with preexistent neurologic autoimmunity experienced irreversible worsening after ICI. CONCLUSIONS: Neural-specific autoantibodies are not uncommon in patients with ICI-related CNS neurologic autoimmunity. Outcomes mostly depend on the pre-ICI treatment characteristics and clinical phenotype.

Original languageEnglish (US)
Pages (from-to)e2442-e2452
JournalNeurology
Volume95
Issue number17
DOIs
StatePublished - Oct 27 2020

ASJC Scopus subject areas

  • Clinical Neurology

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