Predictors for the development of neurological immune-related adverse events of immune checkpoint inhibitors and impact on mortality.
immune checkpoint inhibitors
incidence
mortality
risk factors
Journal
European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
revised:
05
04
2023
received:
06
12
2022
accepted:
19
06
2023
medline:
8
9
2023
pubmed:
23
6
2023
entrez:
23
6
2023
Statut:
ppublish
Résumé
Little is known about risk factors for developing neurological immunological adverse events (neuro-irAEs) from immune checkpoint inhibitors (ICIs). We report the incidence, predictors for development, impact on mortality of neuro-irAEs, and impact of ICIs on pre-existing neurological conditions in a large clinical cohort. Patients who received ICIs between January 2011 and December 2018 were identified from a tertiary cancer center registry. Descriptive statistics were used to summarize patient, cancer, and treatment data. Odds ratios from univariable and multivariable logistic regression models were calculated to identify potential predictors for developing a neuro-irAE. Impact of neuro-irAEs on overall survival was estimated by Kaplan-Meier and Cox proportional hazard models. Overall frequency of neurological irAEs was 2.3%. Peripheral nervous system complications were most frequent (53.6%). Melanoma, younger age, prior chemotherapy, prior resection, CTLA-4 ICIs exposure, and combination PD-1 and CTLA-4 ICIs exposure had significantly higher odds for developing a neuro-irAE (p < 0.05) in univariate but not multivariate models. Those with a neuro-irAE were less likely to die at 3 years compared to those without a neuro-irAE (69% vs. 55%, p = 0.004) in univariate but not multivariate model. Flare of pre-existing neurological condition after exposure to ICIs was present (15.4%, 2 of 13 patients) but manageable. One patient was rechallenged with ICIs without recurrent flare. Neuro-irAEs are not associated with increase in overall mortality. Potential predictors for the development of neuro-irAEs are younger age, melanoma, prior chemotherapy and resection, CTLA-4, or combination ICIs exposure.
Sections du résumé
BACKGROUND AND PURPOSE
Little is known about risk factors for developing neurological immunological adverse events (neuro-irAEs) from immune checkpoint inhibitors (ICIs). We report the incidence, predictors for development, impact on mortality of neuro-irAEs, and impact of ICIs on pre-existing neurological conditions in a large clinical cohort.
METHODS
Patients who received ICIs between January 2011 and December 2018 were identified from a tertiary cancer center registry. Descriptive statistics were used to summarize patient, cancer, and treatment data. Odds ratios from univariable and multivariable logistic regression models were calculated to identify potential predictors for developing a neuro-irAE. Impact of neuro-irAEs on overall survival was estimated by Kaplan-Meier and Cox proportional hazard models.
RESULTS
Overall frequency of neurological irAEs was 2.3%. Peripheral nervous system complications were most frequent (53.6%). Melanoma, younger age, prior chemotherapy, prior resection, CTLA-4 ICIs exposure, and combination PD-1 and CTLA-4 ICIs exposure had significantly higher odds for developing a neuro-irAE (p < 0.05) in univariate but not multivariate models. Those with a neuro-irAE were less likely to die at 3 years compared to those without a neuro-irAE (69% vs. 55%, p = 0.004) in univariate but not multivariate model. Flare of pre-existing neurological condition after exposure to ICIs was present (15.4%, 2 of 13 patients) but manageable. One patient was rechallenged with ICIs without recurrent flare.
CONCLUSIONS
Neuro-irAEs are not associated with increase in overall mortality. Potential predictors for the development of neuro-irAEs are younger age, melanoma, prior chemotherapy and resection, CTLA-4, or combination ICIs exposure.
Substances chimiques
Immune Checkpoint Inhibitors
0
CTLA-4 Antigen
0
Antineoplastic Agents, Immunological
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3221-3227Subventions
Organisme : NCATS NIH HHS
ID : KL2 TR002547
Pays : United States
Informations de copyright
© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
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