Published July 23, 2022
| Version v1
Journal article
MBD4 deficiency is predictive of response to immune checkpoint inhibitors in metastatic uveal melanoma patients.
Creators
- Saint-Ghislain, Mathilde
- Derrien, Anne-Céline
- Geoffrois, Lionnel
- Gastaud, Lauris
- Lesimple, Thierry
- Negrier, Sylvie
- Penel, Nicolas
- Kurtz, Jean-Emmanuel
- Le Corre, Yannick
- Dutriaux, Caroline
- Gardrat, Sophie
- Barnhill, Raymond
- Matet, Alexandre
- Cassoux, Nathalie
- Houy, Alexandre
- Ramtohul, Toulsie
- Servois, Vincent
- Mariani, Pascale
- Piperno-Neumann, Sophie
- Stern, Marc-Henri
- Rodrigues, Manuel
Contributors
Others:
- Institut Curie [Paris]
- Unité de génétique et biologie des cancers (U830) ; Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL) ; UNICANCER
- Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL) ; UNICANCER-Université Côte d'Azur (UniCA)
- CRLCC Eugène Marquis (CRLCC) ; UNICANCER
- Centre Léon Bérard [Lyon]
- Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS) ; Université de Lille-Centre Hospitalier Régional Universitaire [CHU Lille] (CHRU Lille) ; Université de Lille-Université de Lille
- Les Hôpitaux Universitaires de Strasbourg (HUS)
- Centre Hospitalier Universitaire d'Angers (CHU Angers) ; PRES Université Nantes Angers Le Mans (UNAM)
- Hôpital Saint-André
Description
BackgroundMBD4 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.MethodsRetrospective cohort of mUM patients treated with ICI. MBD4 was sequenced in a subset of these patients.ResultsThree 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).ConclusionsIn 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.
Abstract
International audienceAdditional details
Identifiers
- URL
- https://hal.univ-lille.fr/hal-04546411
- URN
- urn:oai:HAL:hal-04546411v1
Origin repository
- Origin repository
- UNICA