Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2025 Jun 2;8(6):e2513727.
doi: 10.1001/jamanetworkopen.2025.13727.

Immune Checkpoint Inhibitors for Patients With Preexisting Autoimmune Neurologic Disorders

Kylie Fletcher  1 , Marc Machaalani  2 , Razane El Hajj Chehade  2 , Amin H Nassar  3 , Rashad Nawfal  2 , Michael Manos  2 , Alexander M Menzies  4   5   6 , Frank Aboubakar-Nana  7 , Jessica C Hassel  8 , David J Pinato  9   10 , Alexandra Johnson  11 , Anna C Olsson-Brown  11 , Matteo S Carlino  4   5   6   12 , Andrea Malgeri  13   14 , Alessio Cortellini  9   13   14 , Aditi Singh  15 , Kaushal Parikh  15 , So Yeon Kim  3 , Abdul Rafeh Naqash  16 , Georgina V Long  4   5   6 , Pavan Challa  3 , Toni K Choueiri  2 , Elad Sharon  2 , Shailee Shah  17   18 , Douglas B Johnson  19
Affiliations
Multicenter Study

Immune Checkpoint Inhibitors for Patients With Preexisting Autoimmune Neurologic Disorders

Kylie Fletcher et al. JAMA Netw Open. .

Abstract

Importance: Immune checkpoint inhibitors (ICIs) are efficacious in many cancer types but can produce immune-related adverse events (irAEs). As such, patients with preexisting autoimmune disorders are often excluded from clinical trials, although subsequent studies have shown that many of these patients have acceptable ICI tolerance. The safety and efficacy of ICIs among patients with preexisting neurologic autoimmune disorders (NAIDs) is not well characterized.

Objective: To evaluate the safety and clinical outcomes associated with ICI therapy among patients with NAIDs.

Design, setting, and participants: This multicenter retrospective cohort study included patients with cancer who were treated with ICIs between October 2013 and May 2023 and had preexisting multiple sclerosis (MS), myasthenia gravis (MG), Guillain-Barré syndrome (GBS), and other NAIDs as well as a control cohort of patients with Parkinson disease (PD).

Exposure: ICI therapy.

Main outcomes and measures: Demographic and clinical characteristics (neurologic disability, active or recent immunosuppression), ICI outcomes (response, progression-free survival [PFS], and overall survival [OS]), and safety outcomes (NAID exacerbation, irAEs) were collected.

Results: A total of 135 patients were included; the median (range) age was 72 (40-88) years, 84 (62%) were men, and 51 (38%) were women. A total of 45 patients had MS; 18, MG; 10, GBS; 5, another NAID; and 57, PD. Exacerbations occurred most frequently in MG (12 of 18 patients [67%]), often resulting in hospitalization (6 [50%]) or death (2 [17%]), with much lower rates in the MS cohort (8 of 45 patients [18%]). Ten patients with a history of GBS tolerated ICI without exacerbations, although 1 developed a fatal case of Lambert Eaton myasthenic syndrome following ICI treatment. No differences in response rate, PFS, or OS were observed between NAID groups.

Conclusions and relevance: In this cohort study of ICI use in NAIDs, patients with MG had frequent and more severe exacerbations, while those with MS had few exacerbations. No obvious differences in survival between groups were observed. ICI may be an option for many patients with appropriate oncologic indications and preexisting NAIDs.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Nasser reported receiving honoraria from the Korean Society of Medical Oncology, Tempus, OncLive, Oklahoma University, and Targeted Oncology; receiving travel compensation from the Korean Society of Medical Oncology and the American Association for Cancer Research; receiving consulting fees from Guidepoint Global, Putnam Associates, and Capvision; receiving compensation from Outlier.ai to provide feedback on data analysis tools and artificial intelligence development; and having equity in Revolution Medicine and Summit Therapeutics outside the submitted work. Dr Menzies reported receiving personal fees for serving on the advisory boards of BMS, MSD, Novartis, Roche, Pierre-Fabre, and QBiotics outside the submitted work. Dr Hassel reported receiving honoraria for talks from BMS, Delcath, Immunocore, MSD, Novartis, Pierre Fabre, Sanofi, and Sunpharma; honoraria for serving on the advisory board of Sunpharma; and grants from BMS, Sunpharma, and Sanofi outside the submitted work. Dr Pinato reported receiving lecture fees from Bayer Healthcare, AstraZeneca, Eisai, BMS, Roche, Ipsen, and OncLive; receiving travel expenses from BMS, Roche, and Bayer Healthcare; receiving consulting fees from Mina Therapeutics, Boeringer Ingelheim, Ewopharma, Eisai, Ipsen, Roche, H3B, AstraZeneca, DaVolterra, Starpharma, Boston Scientific, Mursla, Avammune Therapeutics, LiFT Biosciences, and Exact Sciences; receiving research funding to the institution from MSD, BMS, GSK, and Eisai; and receiving personal fees from ViiV Healthcare and Terumo outside the submitted work. Dr Olsson-Brown reported receiving travel support from Roche and MSD; receiving honoraria from BMS, Eiasi, Bohringer-Inglehiem, Ipsen, Regeneron, GSK, Merck, and Chugai; and receiving travel support and honoraria from AstraZeneca outside the submitted work. Dr Carlino reported receiving personal fees from Amgen, BMS, Eisai, Ideaya, MSD, Nektar, Novartis, Oncosec, Pierre Fabre, QBiotics, Regeneron, Roche, Merck, and Sanofi and receiving honoraria from BMS, MSD, and Novartis outside the submitted work. Dr Cortellini reported receiving personal fees from MSD, AstraZeneca, Roche, Regeneron, BMS, OncoC4, IQVIA, Access Infinity, Ardelis Health, Alpha Sight, Guidepoint, Roche, and Amgen; receiving speaker fees from AstraZeneca, Pierre-Fabre, MSD, and Sanofi/Regeneron; receiving writing or editorial compensation from BMS and MSD; receiving travel support from Sanofi/Regeneron and MSD; and receiving research funding (to the institution) from the International Association for the Study of Lung Cancer outside the submitted work. Dr Parikh reported receiving consulting fees to the institution from Regeneron, Rigel, and AstraZeneca outside the submitted work. Dr Kim reported receiving institutional funding from Genentech, Genmab, BioInvent, AstraZeneca, Boehringer Ingelheim, BMS, MonteRosa, Bridgebio, Seagan, Nykode Therapeutics, Dynamicure, Gilead, Takeda, Vaccibody, and LoxoLilly; serving on the advisory board of Genentech; receiving educational honoraria from Medscape, Onclive, and Dava; and receiving travel support from International Association for the Study of Lung Cancer and Dava outside the submitted work. Dr Naqash reports receiving institutional funding as principal investigator for trials from LoxoLilly, Surface Oncology, ADC Therapeutics, IGM Biosciences, EMD Serono, Aravive, Nikang Therapeutics, Inspirna, Exelexis, Revolution Medicine, Jacobio, Pionyr, Jazz Pharmaceuticals, NGM Biopharmaceuticals, Immunocore, Phanes Therapeutics, and Kymera Therapeutics; receiving compensation for serving as a consultant editor from JCO Precision Oncology; receiving travel compensation from the Society for Immunotherapy of Cancer, American Association for Cancer Research, Conquer Cancer Foundation, BinayTara Foundation, Foundation Med, Caris Life Sciences, the American Society for Clinical Oncology, and Jazz Pharmaceuticals; serving on the advisory boards of Foundation Med, Astellas, and NGM Biosciences; receiving honoraria for educational content from BinayTara Foundation, Foundation Med, and Medlive; and receiving grant support from SWOG Hope Foundation outside the submitted work. Dr Long reported receiving consulting fees from Agenus, Amgen, Array Biopharma, AstraZeneca, Bayer Healthcare, BioNTech, Boehringer Ingleheim, BMS, Evaxion, GI Innovation, Hexal AG, Highlight Therapeutics, Immunocore Ireland, Innovent Biologics, IO Biotech, Iovance Biotherapeutics, MSD, Novartis, PHMR, Pierre Fabre, Regeneron, Scancell, and SkyineDX outside the submitted work. Dr Choueiri reported receiving institutional and personal paid and unpaid support for research, advisory boards, consultancy, and honoraria from Alkermes, Arcus Bio, AstraZeneca, Aravive, Aveo, Bayer, BMS, Bicycle Therapeutics, Calithera, Circle Pharma, Deciphera Pharmaceuticals, Eisai, EMD Serono, Exelixis, GSK, Gilead, HiberCell, IQVA, Infinity, Institut Servier, Ipsen, Jannsen Pharmaceuticals, Kanaph, Eli Lilly and Co, Merck, Nikang, Neomorph, Nuscan/PrecedeBio, Novartis, Oncohost, Pfizer, Roche, Sanofi/Aventis, Scholar Rock, Surface Oncology, Takeda, Tempest, UpToDate, and Xencor outside the submitted work; having institutional patents filed on molecular alterations and immunotherapy response and toxicity, rare genitourinary cancers, and ctDNA/liquids biopsies; holding equity in Tempest, Pionyr, Osel, Precede Bio, CureResponse, InnDura Therapeutics, Primium, Abalytics, and Faron Pharma; serving on committees for National Comprehensive Cancer Network, GU Steering Committee, American Society for Clinical Oncology (board of directors, June 2024), European Society for Medical Oncology, American and Community Cancer Research United, and KidneyCan; serving as a mentor for several non–US citizens on research projects with potential funding from non-US sources or foreign components; receiving support from the Dana-Farber/Harvard Cancer Center Kidney SPORE, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, Pan Mass Challenge, Hinda and Arthur Marcus Fund, and Loker Pinard Funds for Kidney Cancer Research at Dana Farber Cancer Institute. Dr Sharon reported serving on the advisory board of Mallinckrodt Pharmaceuticals and receiving consulting fees from D. E. Shaw Research outside the submitted work. Dr Shah reported serving on the advisory board for Alexion (AstraZeneca), Genentech, Catalyst Pharmaceuticals, and Amgen outside the submitted work. Dr D. B. Johnson reported serving on the advisory boards of AstraZeneca, BMS, Merck, Novartis, and Pfizer; receiving consulting fees from Jackson Labs; receiving personal fees from Mallinckrodt, Mosaic ImmunoEngineering, Teiko; and receiving research funding from BMS and Incyte outside the submitted work; in addition, Dr D. B. Johnson reported having a patent for MHC-II as biomarker of immune response issued and a patent for Abatacept as treatment for severe immune toxicities pending.

Figures

Figure.
Figure.. Survival Outcomes
(A) Progression-free survival and (B) overall survival in patients with neurologic autoimmune disorders myasthenia gravis (MG), multiple sclerosis (MS), Guillain-Barré syndrome (GBS), Parkinson disease (PD), and other neurologic autoimmune disorders.
See this image and copyright information in PMC

References

    1. Fessas P, Possamai LA, Clark J, et al. . Immunotoxicity from checkpoint inhibitor therapy: clinical features and underlying mechanisms. Immunology. 2020;159(2):167-177. - PMC - PubMed
    1. Johnson DB, Chandra S, Sosman JA. Immune checkpoint inhibitor toxicity in 2018. JAMA. 2018;320(16):1702-1703. doi:10.1001/jama.2018.13995 - DOI - PubMed
    1. Johnson DB, Sullivan RJ, Menzies AM. Immune checkpoint inhibitors in challenging populations. Cancer. 2017;123(11):1904-1911. doi:10.1002/cncr.30642 - DOI - PMC - PubMed
    1. Johnson DB, Sullivan RJ, Ott PA, et al. . Ipilimumab therapy in patients with advanced melanoma and preexisting autoimmune disorders. JAMA Oncol. 2016;2(2):234-240. doi:10.1001/jamaoncol.2015.4368 - DOI - PubMed
    1. Menzies AM, Johnson DB, Ramanujam S, et al. . Anti-PD-1 therapy in patients with advanced melanoma and preexisting autoimmune disorders or major toxicity with ipilimumab. Ann Oncol. 2017;28(2):368-376. doi:10.1093/annonc/mdw443 - DOI - PMC - PubMed

Publication types

Substances