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EZH2 Y641 des mutations actives de hotspot se produisent dans ~20-25% du lymphome folliculaire (et rare...

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IDBMA-EZH2-Y641-FL
TypePertinence thérapeutique
Étatreviewed 2026-04-27 | pending_clinical_signoff | actionability review required
MaladiesDIS-FL
SourcesSRC-CIVIC SRC-ESMO-FL-2024 SRC-NCCN-BCELL-2025

Faits relatifs à l ' action en justice

BiomarqueurBIO-EZH2-Y641
VarianteY641N/F/H/S/C activant les mutations dans le domaine SET — gain de fonction hyperméthylation H3K27; ~20-25% du lymphome folliculaire
MaladieDIS-FL
Niveau ESCATIB
Combinaisons recommandéestazemetostat monotherapy (R/R EZH2-mutated FL after ≥2 prior systemic therapies per SRC-NCCN-BCELL-2025, SRC-ESMO-FL-2024)
Résumé des faitsEZH2 Y641 hotspot activating mutations occur in ~20-25% of follicular lymphoma (and rarely in DLBCL/HGBL). Tazemetostat is a selective EZH2 inhibitor FDA-approved for relapsed/refractory FL: in EZH2- mutated FL after ≥2 prior lines, ORR 69%, mPFS 13.8 mo (E7438-202 Morschhauser Lancet Oncol 2020); in EZH2-WT FL, ORR 35%, mPFS 11.1 mo — mutated population had stronger responses, leading to a companion-diagnostic-paired indication per SRC-NCCN-BCELL-2025, SRC-ESMO-FL-2024.

Notes

ESCAT IB / OncoKB Level 1. cobas EZH2 Mutation Test is the companion diagnostic. EZH2-WT subset has FDA approval as well but with ~halved ORR — mutation testing improves selection per ESMO 2024. EZH2-Y641 in DLBCL: investigational; not approved (DLBCL trials in combination with R-CHOP have not yet read out positively per SRC-NCCN-BCELL-2025). Source-gap: SRC-E7438-202 (Morschhauser 2020) not yet ingested.

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