MBD4 deficiency is predictive of response to immune checkpoint inhibitors in metastatic uveal melanoma patients. - Université de Lille Accéder directement au contenu
Article Dans Une Revue European Journal of Cancer Care Année : 2022

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

Résumé

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.
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Dates et versions

hal-04546411 , version 1 (15-04-2024)

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Mathilde Saint-Ghislain, Anne-Céline Derrien, Lionnel Geoffrois, Lauris Gastaud, Thierry Lesimple, et al.. MBD4 deficiency is predictive of response to immune checkpoint inhibitors in metastatic uveal melanoma patients.. European Journal of Cancer Care, 2022, European Journal of Cancer Care, 173, pp.105-112. ⟨10.1016/j.ejca.2022.06.033⟩. ⟨hal-04546411⟩
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