Titre :

MBD4 deficiency is predictive of response to immune checkpoint inhibitors in metastatic uveal melanoma patients.

Auteur(s) :

Saint-Ghislain, Mathilde [Auteur]
Institut Curie [Paris]
Derrien, Anne-Céline [Auteur]
Unité de génétique et biologie des cancers [U830]
Geoffrois, Lionnel [Auteur]
Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] [UNICANCER/ICL]
Gastaud, Lauris [Auteur]
Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] [UNICANCER/CAL]
Lesimple, Thierry [Auteur]
CRLCC Eugène Marquis [CRLCC]
Negrier, Sylvie [Auteur]
Centre Léon Bérard [Lyon]
Penel, Nicolas [Auteur]
METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694
Kurtz, Jean-Emmanuel [Auteur]
Les Hôpitaux Universitaires de Strasbourg [HUS]
Le Corre, Yannick [Auteur]
Centre Hospitalier Universitaire d'Angers [CHU Angers]
Dutriaux, Caroline [Auteur]
Hôpital Saint-André
Gardrat, Sophie [Auteur]
Institut Curie [Paris]
Barnhill, Raymond [Auteur]
Institut Curie [Paris]
Matet, Alexandre [Auteur]
Institut Curie [Paris]
Cassoux, Nathalie [Auteur]
Institut Curie [Paris]
Houy, Alexandre [Auteur]
Unité de génétique et biologie des cancers [U830]
Ramtohul, Toulsie [Auteur]
Institut Curie [Paris]
Servois, Vincent [Auteur]
Institut Curie [Paris]
Mariani, Pascale [Auteur]
Institut Curie [Paris]
Piperno-Neumann, Sophie [Auteur]
Institut Curie [Paris]
Stern, Marc-Henri [Auteur]
Unité de génétique et biologie des cancers [U830]
Institut Curie [Paris]
Rodrigues, Manuel [Auteur]
Unité de génétique et biologie des cancers [U830]

Titre de la revue :

European Journal of Cancer Care

Nom court de la revue :

Eur J Cancer

Numéro :

173

Pagination :

105-112

Date de publication :

2022-07-23

ISSN :

1879-0852

Mot(s)-clé(s) en anglais :

MBD4
Hypermutation
Mutational process
Immune checkpoint inhibitor
PD-1
PD-L1
Predictive biomarker

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Background MBD4 mutations have been reported in uveal melanomas, acute myeloid leukemias, colorectal adenocarcinomas, gliomas, and spiradenocarcinomas and cause a hypermutated phenotype. Although metastatic uveal melanomas ...
Lire la suite >Background MBD4 mutations have been reported in uveal melanomas, acute myeloid leukemias, colorectal adenocarcinomas, gliomas, and spiradenocarcinomas and cause a hypermutated phenotype. Although metastatic uveal melanomas (mUM) are usually resistant to immune checkpoint inhibitors (ICI), the first reported MBD4-mutated (MBD4m) patient responded to ICI, suggesting that MBD4 mutation may predict response to ICI. Methods Retrospective cohort of mUM patients treated with ICI. MBD4 was sequenced in a subset of these patients. Results Three hundred mUM patients were included. Median follow-up was 17.3 months. Ten patients with an objective response and 20 cases with stable disease for >12 months were observed, corresponding to an objective response rate of 3.3% and a clinical benefit (i.e., responder patients and stable disease) rate of 10%. Of the 131 tumors sequenced for MBD4, five (3.8%) were mutated. MBD4 mutation was associated with a better objective response rate as three out of five MBD4m versus 4% of MBD4 wild-type patients responded (p < 0.001). Of these five responders, three presented progressive disease at 2.8, 13.9, and 22.3 months. Median PFS was 4.0 months in MBD4 wild-type and 22.3 months in MBD4m patients (HR = 0.22; p = 0.01). Median OS in MBD4def patients was unreached as compared to 16.6 months in MBD4pro (HR = 0.11; 95% CI: 0.02–0.86; log-rank p-test = 0.04; Fig. 2e). Conclusions In mUM patients, MBD4 mutation is highly predictive for the response, PFS, and overall survival benefit to ICI. MBD4 could be a tissue-agnostic biomarker and should be sequenced in mUM, and other tumor types where MBD4 mutations are reported.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
CHU Lille

Collections :

• METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694

Date de dépôt :

2023-11-15T03:40:41Z
2024-04-15T09:11:35Z