Diagnostic and prognostic biomarkers in immune checkpoint inhibitor-related encephalitis: a retrospective cohort study.
Adverse events
Autoimmune encephalitis
Biomarkers
Cancer
Cancer immunotherapy
Encephalitis
Immune checkpoint inhibitors
Neural antibodies
Neurological immune-related adverse events
Paraneoplastic neurological syndromes
Prognostic factors
Journal
The Lancet regional health. Europe
ISSN: 2666-7762
Titre abrégé: Lancet Reg Health Eur
Pays: England
ID NLM: 101777707
Informations de publication
Date de publication:
Sep 2024
Sep 2024
Historique:
received:
07
04
2024
revised:
06
07
2024
accepted:
11
07
2024
medline:
22
8
2024
pubmed:
22
8
2024
entrez:
22
8
2024
Statut:
epublish
Résumé
Immune checkpoint inhibitor-related encephalitis (ICI-encephalitis) is not well characterised and diagnostic and prognostic biomarkers are lacking. We aimed to comprehensively characterise ICI-encephalitis and identify diagnostic biomarkers and outcome predictors. This retrospective observational study included all patients with ICI-encephalitis studied in the French Reference Centre on Paraneoplastic Neurological Syndromes (PNS) and Autoimmune Encephalitis (2015-2023). ICI encephalitis was considered definite in case of inflammatory findings at paraclinical tests and/or well-characterised neural antibodies. Predictors of immune-related adverse event (irAE) treatment response, defined as a Common Terminology Criteria for Adverse Events v5.0 grade < 3 at any time after therapeutic intervention, were assessed by logistic regression analysis, and predictors of mortality by Cox regression analysis. Neurofilament light chain (NfL) was measured by enzyme-linked immunosorbent assay. Sixty-seven patients with definite encephalitis were identified (median age, 69 years; 66% male). A focal syndrome was observed in 43/67 patients (64%; limbic encephalitis, cerebellar ataxia, and/or brainstem encephalitis), while 24/67 (36%) had meningoencephalitis, a non-focal syndrome with altered mental status (22/24 patients, 92%) and pleocytosis (24/24 patients, 100%). Patients with focal encephalitis more frequently had abnormal brain MRI (26/42, 62% ICI-encephalitis corresponds to a set of clinically-recognisable syndromes. Patients with focal encephalitis, PNS-related antibodies, and/or higher serum NfL have low irAE treatment response rates. Research is needed on the underlying immunopathogenesis to foster therapeutic innovations. Agence Nationale de la Recherche.
Sections du résumé
Background
UNASSIGNED
Immune checkpoint inhibitor-related encephalitis (ICI-encephalitis) is not well characterised and diagnostic and prognostic biomarkers are lacking. We aimed to comprehensively characterise ICI-encephalitis and identify diagnostic biomarkers and outcome predictors.
Methods
UNASSIGNED
This retrospective observational study included all patients with ICI-encephalitis studied in the French Reference Centre on Paraneoplastic Neurological Syndromes (PNS) and Autoimmune Encephalitis (2015-2023). ICI encephalitis was considered definite in case of inflammatory findings at paraclinical tests and/or well-characterised neural antibodies. Predictors of immune-related adverse event (irAE) treatment response, defined as a Common Terminology Criteria for Adverse Events v5.0 grade < 3 at any time after therapeutic intervention, were assessed by logistic regression analysis, and predictors of mortality by Cox regression analysis. Neurofilament light chain (NfL) was measured by enzyme-linked immunosorbent assay.
Findings
UNASSIGNED
Sixty-seven patients with definite encephalitis were identified (median age, 69 years; 66% male). A focal syndrome was observed in 43/67 patients (64%; limbic encephalitis, cerebellar ataxia, and/or brainstem encephalitis), while 24/67 (36%) had meningoencephalitis, a non-focal syndrome with altered mental status (22/24 patients, 92%) and pleocytosis (24/24 patients, 100%). Patients with focal encephalitis more frequently had abnormal brain MRI (26/42, 62%
Interpretation
UNASSIGNED
ICI-encephalitis corresponds to a set of clinically-recognisable syndromes. Patients with focal encephalitis, PNS-related antibodies, and/or higher serum NfL have low irAE treatment response rates. Research is needed on the underlying immunopathogenesis to foster therapeutic innovations.
Funding
UNASSIGNED
Agence Nationale de la Recherche.
Identifiants
pubmed: 39170102
doi: 10.1016/j.lanepe.2024.101011
pii: S2666-7762(24)00178-9
pmc: PMC11338149
doi:
Types de publication
Journal Article
Langues
eng
Pagination
101011Informations de copyright
© 2024 The Author(s).
Déclaration de conflit d'intérêts
AF, MVG, BJ, and JH are supported by BETPSY, project as part of the second Investissements d'Avenir programme (ANR-18-RHUS-0012) supported by a public grant overseen by the Agence Nationale de la Recherche (ANR). AF received a grant to perform research abroad by the European Academy of Neurology. MVG is supported by Fundación Martín Escudero (non-profit Spanish foundation) to perform research abroad. JH receives royalties from licensing fees to Athena Diagnostics, Euroimmun, and ravo Diagnostika for a patent for the use of anti-CV2/CRMP5 as diagnostic tests. All other authors declare no competing interests.