PT  - JOURNAL ARTICLE
AU  - Elia Sechi
AU  - Svetomir N. Markovic
AU  - Andrew McKeon
AU  - Divyanshu Dubey
AU  - Teerin Liewluck
AU  - Vanda A. Lennon
AU  - A. Sebastian Lopez-Chiriboga
AU  - Christopher J. Klein
AU  - Michelle Mauermann
AU  - Sean J. Pittock
AU  - Eoin P. Flanagan
AU  - Anastasia Zekeridou
TI  - Neurologic autoimmunity and immune checkpoint inhibitors
AID  - 10.1212/WNL.0000000000010632
DP  - 2020 Oct 27
TA  - Neurology
PG  - e2442--e2452
VI  - 95
IP  - 17
4099  - http://n.neurology.org/content/95/17/e2442.short
4100  - http://n.neurology.org/content/95/17/e2442.full
SO  - Neurology2020 Oct 27; 95
AB  - 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.AChR=acetylcholine receptor; ANNA=antineuronal nuclear antibody; BDUMP=bilateral diffuse uveal melanocytic proliferation; CRMP5=collapsin response-mediator protein 5; CTLA4=cytotoxic T-lymphocyte–associated antigen-4; GAD65=glutamic acid decarboxylase 65; GFAP=glial fibrillary acidic protein; HMGCR=β-hydroxy-β-methylglutaryl coenzyme-A reductase; ICI=immune checkpoint inhibitor; IgG=immunoglobulin G; IVIg=IV immunoglobulin; LGI1=leucine-rich glioma-inactivated 1; MG=myasthenia gravis; NIF=neuronal intermediate filament; NMDAR=NMDA receptor; PCA=Purkinje cell antibody; PD1=programmed death-1; PDL1=programmed death-1 ligand; PRES=posterior reversible encephalopathy syndrome; SCLC=small-cell lung carcinoma; SRP=signal recognition particle; STR=striational autoantibodies; UNA=autoantibodies as yet unidentified molecularly; VGCC=voltage-gated calcium channels; VGKC=voltage-gated potassium channel