Immune Checkpoint Inhibitors for Patients With Preexisting Autoimmune Neurologic Disorders

Kylie Fletcher; Marc Machaalani; Razane El Hajj Chehade; Amin H Nassar; Rashad Nawfal; Michael Manos; Alexander M Menzies; Frank Aboubakar-Nana; Jessica C Hassel; David J Pinato; Alexandra Johnson; Anna C Olsson-Brown; Matteo S Carlino; Andrea Malgeri; Alessio Cortellini; Aditi Singh; Kaushal Parikh; So Yeon Kim; Abdul Rafeh Naqash; Georgina V Long; Pavan Challa; Toni K Choueiri; Elad Sharon; Shailee Shah; Douglas B Johnson

doi:10.1001/jamanetworkopen.2025.13727

Immune Checkpoint Inhibitors for Patients With Preexisting Autoimmune Neurologic Disorders

Kylie Fletcher
, Marc Machaalani
, Razane El Hajj Chehade
, Amin H Nassar
, Rashad Nawfal
, Michael Manos
, Alexander M Menzies
, Frank Aboubakar-Nana
, Jessica C Hassel
, David J Pinato
, Alexandra Johnson
, Anna C Olsson-Brown
, Matteo S Carlino
, Andrea Malgeri
, Alessio Cortellini
, Aditi Singh
, Kaushal Parikh
, So Yeon Kim
, Abdul Rafeh Naqash
, Georgina V Long

Pavan Challa, Toni K Choueiri, Elad Sharon, Shailee Shah, Douglas B Johnson

Cork University Dental School and Hospital

Vanderbilt University School of Medicine
Dana-Farber Cancer Institute
Yale University
The University of Sydney
Service de Pneumologie
University Hospital Heidelberg
Imperial College London
Clatterbridge Cancer Centre NHS Foundation Trust
Fondazione Policlinico Universitario Campus-Biomedico
Department of Oncology
The University of Oklahoma Health Sciences
Northwestern University
Vanderbilt University Medical Center

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	e2513727
Pages (from-to)	e2513727
Journal	JAMA Network Open
Volume	8
Issue number	6
DOIs	https://doi.org/10.1001/jamanetworkopen.2025.13727
Publication status	Published - 4 Jun 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Adult
Aged
Aged, 80 and over
Autoimmune Diseases of the Nervous System/drug therapy
Autoimmune Diseases/drug therapy
Female
Humans
Immune Checkpoint Inhibitors/therapeutic use
Male
Middle Aged
Neoplasms/drug therapy
Retrospective Studies

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10.1001/jamanetworkopen.2025.13727

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Fletcher, K., Machaalani, M., El Hajj Chehade, R., Nassar, A. H., Nawfal, R., Manos, M., Menzies, A. M., Aboubakar-Nana, F., Hassel, J. C., Pinato, D. J., Johnson, A., Olsson-Brown, A. C., Carlino, M. S., Malgeri, A., Cortellini, A., Singh, A., Parikh, K., Kim, S. Y., Naqash, A. R., ... Johnson, D. B. (2025). Immune Checkpoint Inhibitors for Patients With Preexisting Autoimmune Neurologic Disorders. JAMA Network Open, 8(6), e2513727. Article e2513727. https://doi.org/10.1001/jamanetworkopen.2025.13727

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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-Barr{\'e} 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.",

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author = "Kylie Fletcher and Marc Machaalani and \{El Hajj Chehade\}, Razane and Nassar, \{Amin H\} and Rashad Nawfal and Michael Manos and Menzies, \{Alexander M\} and Frank Aboubakar-Nana and Hassel, \{Jessica C\} and Pinato, \{David J\} and Alexandra Johnson and Olsson-Brown, \{Anna C\} and Carlino, \{Matteo S\} and Andrea Malgeri and Alessio Cortellini and Aditi Singh and Kaushal Parikh and Kim, \{So Yeon\} and Naqash, \{Abdul Rafeh\} and Long, \{Georgina V\} and Pavan Challa and Choueiri, \{Toni K\} and Elad Sharon and Shailee Shah and Johnson, \{Douglas B\}",

year = "2025",

month = jun,

day = "4",

doi = "10.1001/jamanetworkopen.2025.13727",

language = "English",

volume = "8",

pages = "e2513727",

journal = "JAMA Network Open",

issn = "2574-3805",

publisher = "American Medical Association",

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Fletcher, K, Machaalani, M, El Hajj Chehade, R, Nassar, AH, Nawfal, R, Manos, M, Menzies, AM, Aboubakar-Nana, F, Hassel, JC, Pinato, DJ, Johnson, A, Olsson-Brown, AC, Carlino, MS, Malgeri, A, Cortellini, A, Singh, A, Parikh, K, Kim, SY, Naqash, AR, Long, GV, Challa, P, Choueiri, TK, Sharon, E, Shah, S & Johnson, DB 2025, 'Immune Checkpoint Inhibitors for Patients With Preexisting Autoimmune Neurologic Disorders', JAMA Network Open, vol. 8, no. 6, e2513727, pp. e2513727. https://doi.org/10.1001/jamanetworkopen.2025.13727

TY - JOUR

T1 - Immune Checkpoint Inhibitors for Patients With Preexisting Autoimmune Neurologic Disorders

AU - Fletcher, Kylie

AU - Machaalani, Marc

AU - El Hajj Chehade, Razane

AU - Nassar, Amin H

AU - Nawfal, Rashad

AU - Manos, Michael

AU - Menzies, Alexander M

AU - Aboubakar-Nana, Frank

AU - Hassel, Jessica C

AU - Pinato, David J

AU - Johnson, Alexandra

AU - Olsson-Brown, Anna C

AU - Carlino, Matteo S

AU - Malgeri, Andrea

AU - Cortellini, Alessio

AU - Singh, Aditi

AU - Parikh, Kaushal

AU - Kim, So Yeon

AU - Naqash, Abdul Rafeh

AU - Long, Georgina V

AU - Challa, Pavan

AU - Choueiri, Toni K

AU - Sharon, Elad

AU - Shah, Shailee

AU - Johnson, Douglas B

PY - 2025/6/4

Y1 - 2025/6/4

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Autoimmune Diseases of the Nervous System/drug therapy

KW - Autoimmune Diseases/drug therapy

KW - Female

KW - Humans

KW - Immune Checkpoint Inhibitors/therapeutic use

KW - Male

KW - Middle Aged

KW - Neoplasms/drug therapy

KW - Retrospective Studies

UR - https://www.scopus.com/pages/publications/105007792893

U2 - 10.1001/jamanetworkopen.2025.13727

DO - 10.1001/jamanetworkopen.2025.13727

M3 - Article

C2 - 40465294

SN - 2574-3805

VL - 8

SP - e2513727

JO - JAMA Network Open

JF - JAMA Network Open

IS - 6

M1 - e2513727

ER -

Immune Checkpoint Inhibitors for Patients With Preexisting Autoimmune Neurologic Disorders

Abstract

UN SDGs

Keywords

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