Immune-related encephalitis after immune checkpoint inhibitor therapy

Monica W Buckley; Aanika Balaji Warner; Julie Brahmer; Laura C Cappelli; William H Sharfman; Ephraim Fuchs; Hyunseok Kang; Patrick M Forde; Douglas E Gladstone; Richard Ambinder; Ronan J Kelly; Evan J Lipson; Ivana Gojo; Edward J Lee; Tory P Johnson; Shiv Saidha; Rafael Llinas; Lyle W Ostrow; Jarushka Naidoo; John C Probasco

doi:10.1093/oncolo/oyae186

Immune-related encephalitis after immune checkpoint inhibitor therapy

Oncologist. 2024 Jul 26:oyae186. doi: 10.1093/oncolo/oyae186. Online ahead of print.

Authors

Monica W Buckley^{1

2}, Aanika Balaji Warner^{3

4}, Julie Brahmer^{3

4}, Laura C Cappelli^{3

5}, William H Sharfman^{3

4}, Ephraim Fuchs³, Hyunseok Kang^{3

6}, Patrick M Forde^{3

4}, Douglas E Gladstone^{3

7}, Richard Ambinder³, Ronan J Kelly^{3

8}, Evan J Lipson^{3

4}, Ivana Gojo³, Edward J Lee⁹, Tory P Johnson¹, Shiv Saidha¹, Rafael Llinas¹, Lyle W Ostrow^{1

10}, Jarushka Naidoo^{3

4

11

12}, John C Probasco¹

Affiliations

¹ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.
² Department of Neurology, University of Virginia School of Medicine, Charlottesville, VA 22903, United States.
³ Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.
⁴ Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, United States.
⁵ Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.
⁶ Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, United States.
⁷ R.J. Zuckerberg Cancer Center at Hofstra/Northwell Health, Lake Success, NY 11042, United States.
⁸ Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX 75246, United States.
⁹ Maryland Oncology Hematology, Columbia, MD 21044, United States.
¹⁰ Department of Neurology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, United States.
¹¹ Department of Oncology, Johns Hopkins Bayview Medical Center, Baltimore, MD 21224, United States.
¹² Department of Medicine, Beaumont Hospital Dublin and RCSI University of Health Sciences, Dublin, 9, Ireland.

PMID: 39066587
DOI: 10.1093/oncolo/oyae186

Abstract

Background: Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment but can trigger immune-related encephalitis. We report one of the largest case series of patients with immune-related encephalitis and review of the literature.

Methods: Retrospective series of patients with immune-related encephalitis and literature review.

Results: Fourteen patients with cancer treated with ICI (50% combination therapy) developed immune-related encephalitis. Diagnostic testing revealed cerebral spinal fluid (CSF) lymphocytic pleocytosis (85%) and elevated protein (69%), abnormal brain magnetic resonance imaging(MRI) (33%) or brain FDG-PET (25%), electroencephalogram (EEG) abnormalities (30%), and autoantibodies (31%). Encephalitis treatment included: corticosteroids (86%), intravenous immunoglobulin (IVIg) (36%), plasmapheresis (7%), and rituximab (29%). There were no deaths and 12 patients had significant recovery, although long-term complications were observed. All patients discontinued ICI. Longitudinal follow-up demonstrated anti-cancer response to ICI at 3 months (85%) and 6 months post-ICI initiation (77%). A literature review identified 132 patients with immune-related encephalitis. Most were treated with PD-1 inhibitors (18% combination). Common abnormalities included elevated CSF protein (84%) or pleocytosis (77%), abnormal brain MRI (65%), or autoantibodies (47%). Nearly all were treated with corticosteroids, many required additional therapy with IVIg (26%) or rituximab (12%). Most patients had clinical improvement (81%) but a minority (10%) had a clinical relapse after completing corticosteroid taper. ICIs were resumed in 7 patients (5%), with relapse in 3.

Conclusions and relevance: Immune-related encephalitis is treatable and improves with corticosteroids in most cases but may require additional immunosuppression. Re-emergence of encephalitis is rare and does not typically result in adverse outcomes, and this should be considered in neurological immune-related adverse event management guidelines.

Keywords: autoimmune; cancer; encephalitis; immune checkpoint.

Abstract

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