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. 2025 Jan 17;30(1):oyae186.
doi: 10.1093/oncolo/oyae186.

Immune-related encephalitis after immune checkpoint inhibitor therapy

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 Fuchs  3 , Hyunseok Kang  3   6 , Patrick M Forde  3   4 , Douglas E Gladstone  3   7 , Richard Ambinder  3 , Ronan J Kelly  3   8 , Evan J Lipson  3   4 , Ivana Gojo  3 , Edward J Lee  9 , Tory P Johnson  1 , Shiv Saidha  1 , Rafael Llinas  1 , Lyle W Ostrow  1   10 , Jarushka Naidoo  3   4   11   12 , John C Probasco  1
Affiliations

Immune-related encephalitis after immune checkpoint inhibitor therapy

Monica W Buckley et al. Oncologist. .

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.

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Figures

Figure 1.
Figure 1.
MRI and brain FDG-PET imaging of patients with immune-related encephalitis. (A) T2/FLAIR MRI brain images at presentation and follow up after treatment in a patient with typical imaging findings of autoimmune encephalitis (patient 9). Note T2/FLAIR hyperintensities of the left hippocampus, left frontal lobe, and posterior cingulate. The left hippocampal lesion evolves to medial temporal sclerosis while the left frontal and posterior cingulate lesions resolve. (B) T2 FLAIR and T1-post-gadolinium MRI brain images at presentation and after treatment in patient with lesion of the right corona radiate demonstrating persistence of T2/FLAIR hyperintensity with resolution of gadolinium enhancement on follow-up (patient 6). (C) FDG-PET/CT brain imaging 112 days prior to and 99 days after immunosuppressive treatment initiation for immune-related encephalitis demonstrating hypermetabolism of the left medial temporal lobe that was not evident on the pre-encephalitis FDG-PET performed through the course of oncologic care (patient 9).
See this image and copyright information in PMC

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