Abstract Details

Title Diagnostic and Prognostic Biomarkers in Immune Checkpoint Inhibitor-Related Encephalitis: a Retrospective Cohort Study

Topic Autoimmune Neurology

Presentation(s) S18 - Paraneoplastic Neurological Disorders, irAE, Stiff Person, IGLON5 (1:48 PM-2:00 PM)

Poster/Presentation
Number 005

Background Immune checkpoint inhibitor-related encephalitis (ICI-encephalitis) is not well characterised and diagnostic and prognostic biomarkers are lacking.

Objective We aimed to comprehensively characterise ICI-encephalitis and identify diagnostic biomarkers and outcome predictors.

Design/Methods This retrospective study included all patients with ICI-encephalitis studied in a national reference center (2015–2023). Treatment response predictors, defined as a CTCAE v5.0 grade < 3 at any time after therapeutic intervention, were assessed by logistic regression analysis, and predictors of mortality by Cox regression analysis. NfL was measured by ELISA.

Results Of 67 patients with definite encephalitis (median age, 69 years; 66% male), 43/67 had a focal syndrome (64%; limbic encephalitis, cerebellar ataxia, and/or brainstem encephalitis), 24/67 (36%) had meningoencephalitis, a non-focal syndrome with altered mental status (22/24, 92%) and pleocytosis (24/24, 100%). Patients with focal encephalitis more frequently had abnormal brain MRI (26/42, 62% versus 8/24, 33%, p = 0.025), PNS-related antibodies (36/43, 84% versus 1/24, 4%, p < 0.001), and neuroendocrine cancers (22/43, 51% versus 1/24, 4%; p < 0.001) than patients with meningoencephalitis. PNS-related antibodies were associated with less treatment response, independently of age, sex, and baseline severity (adjusted OR 0.05; 95%CI [0.01; 0.19]; p < 0.001) as well as higher mortality, independently of age and cancer type (adjusted HR 5.07; 95% CI [2.12; 12.12]; p < 0.001). Serum NfL discriminated patients with definite ICI-encephalitis (n = 27) from cancer-matched controls (n = 16; optimal cut-off >273.5 pg/mL, sensitivity 81%, specificity 88%, AUC 0.87, 95% CI [0.76; 0.98]) and irAE treatment responders (n = 10) from non-responders (n = 17, optimal cut-off >645 pg/mL, sensitivity 90%, specificity 65%; AUC 0.75, 95% CI [0.55; 0.94]).

Conclusions ICI-encephalitis corresponds to a set of clinically-recognisable syndromes. Patients with focal encephalitis, PNS-related antibodies, and/or higher serum NfL have low treatment response rates. Research is needed on the underlying immunopathogenesis to foster therapeutic innovations.

Authors/Disclosures
Antonio Farina PRESENTER	Mr. Farina has nothing to disclose.
Macarena Villagran-Garcia, MD	Dr. Villagran-Garcia has received research support from Fundación Martín Escudero.
Anne-Laurie Pinto	Anne-Laurie Pinto has nothing to disclose.
Marie Benaiteau, MD	Dr. Benaiteau has nothing to disclose.
Birzu Cristina, MD	Dr. Cristina has nothing to disclose.
pauline dumez, MD	Dr. dumez has nothing to disclose.
Dimitri Psimaras, MD (Hopital Salpetrière ; Service)	No disclosure on file
Marie Rafiq, MD	Dr. Rafiq has nothing to disclose.
GERALDINE PICARD, MSc	Mrs. PICARD has nothing to disclose.
Virginie Desestret	Virginie Desestret has nothing to disclose.
Jerome Honnorat, MD, PhD (Hospices Civils de Lyon)	The institution of Jerome Honnorat, MD, PhD has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for journal of neurology.
Bastien Joubert	Bastien Joubert has nothing to disclose.

��ɫ��

��ɫ��