Elia Sechi1, Svetomir N Markovic1, Andrew McKeon1, Divyanshu Dubey1, Teerin Liewluck1, Vanda A Lennon1, A Sebastian Lopez-Chiriboga1, Christopher J Klein1, Michelle Mauermann1, Sean J Pittock1, Eoin P Flanagan1, Anastasia Zekeridou2. 1. From the Departments of Neurology (E.S., A.M., D.D., T.L., V.A.L., C.J.K., M.M., S.J.P., E.P.F., A.Z.), Oncology (S.N.M.), Laboratory Medicine and Pathology (A.M., D.D., V.A.L., S.J.P., E.P.F., A.Z.), and Immunology (V.A.L.), Mayo Clinic, Rochester, MN; and Department of Neurology (A.S.L.-C.), Mayo Clinic, Jacksonville, FL. 2. From the Departments of Neurology (E.S., A.M., D.D., T.L., V.A.L., C.J.K., M.M., S.J.P., E.P.F., A.Z.), Oncology (S.N.M.), Laboratory Medicine and Pathology (A.M., D.D., V.A.L., S.J.P., E.P.F., A.Z.), and Immunology (V.A.L.), Mayo Clinic, Rochester, MN; and Department of Neurology (A.S.L.-C.), Mayo Clinic, Jacksonville, FL. zekeridou.anastasia@mayo.edu.
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.
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.
Authors: S Cuzzubbo; F Javeri; M Tissier; A Roumi; C Barlog; J Doridam; C Lebbe; C Belin; R Ursu; A F Carpentier Journal: Eur J Cancer Date: 2017-01-05 Impact factor: 9.162
Authors: Divyanshu Dubey; William S David; Anthony A Amato; Kerry L Reynolds; Nathan F Clement; Donald F Chute; Justine V Cohen; Donald P Lawrence; Meghan J Mooradian; Ryan J Sullivan; Amanda C Guidon Journal: Neurology Date: 2019-08-12 Impact factor: 9.910
Authors: Julie R Brahmer; Christina Lacchetti; Bryan J Schneider; Michael B Atkins; Kelly J Brassil; Jeffrey M Caterino; Ian Chau; Marc S Ernstoff; Jennifer M Gardner; Pamela Ginex; Sigrun Hallmeyer; Jennifer Holter Chakrabarty; Natasha B Leighl; Jennifer S Mammen; David F McDermott; Aung Naing; Loretta J Nastoupil; Tanyanika Phillips; Laura D Porter; Igor Puzanov; Cristina A Reichner; Bianca D Santomasso; Carole Seigel; Alexander Spira; Maria E Suarez-Almazor; Yinghong Wang; Jeffrey S Weber; Jedd D Wolchok; John A Thompson Journal: J Clin Oncol Date: 2018-02-14 Impact factor: 44.544
Authors: Michael P Brown; Pravin Hissaria; Amy Hc Hsieh; Christopher Kneebone; Wilson Vallat Journal: J Neuroimmunol Date: 2017-01-18 Impact factor: 3.478
Authors: Avi Fellner; Chen Makranz; Michal Lotem; Felix Bokstein; Alisa Taliansky; Shai Rosenberg; Deborah T Blumenthal; Jacob Mandel; Suzana Fichman; Elena Kogan; Israel Steiner; Tali Siegal; Alexander Lossos; Shlomit Yust-Katz Journal: J Neurooncol Date: 2018-01-13 Impact factor: 4.130
Authors: Elia Sechi; Laura Cacciaguerra; John J Chen; Sara Mariotto; Giulia Fadda; Alessandro Dinoto; A Sebastian Lopez-Chiriboga; Sean J Pittock; Eoin P Flanagan Journal: Front Neurol Date: 2022-06-17 Impact factor: 4.086