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MYD88 L265P present in >90% of WM. Activates NF-κB via BTK/IRAK signaling — rationale for...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

IDBMA-MYD88-L265P-WM
TypeActionability
Statusreviewed 2026-04-27 | pending_clinical_signoff | actionability review required
DiseasesDIS-WM
SourcesSRC-CIVIC SRC-ESMO-WM-2024 SRC-NCCN-BCELL-2025

Actionability Facts

BiomarkerBIO-MYD88-L265P
VariantL265P
DiseaseDIS-WM
ESCAT tierIA
Recommended combinationszanubrutinib (preferred per ASPEN — fewer cardiac AE vs ibrutinib), ibrutinib monotherapy, ibrutinib + rituximab, BR (chemo-immuno alternative)
Evidence summaryMYD88 L265P present in >90% of WM. Activates NF-κB via BTK/IRAK signaling — rationale for BTKi. Ibrutinib monotherapy (iNNOVATE substudy 2 / arm A — Treon et al. NEJM 2015 R/R; iNNOVATE — Dimopoulos et al. NEJM 2018 1L+R/R with rituximab) and zanubrutinib (ASPEN — Tam et al. Blood 2020) FDA-approved. CXCR4 WHIM-like co-mutation reduces but does not abolish response.

Notes

ESCAT IA. OncoKB Level 1. CXCR4 WHIM-like mutation testing recommended as it modulates BTKi response. MYD88-WT WM (~10%) responds less well to BTKi.

Used By

No reverse references found in the YAML corpus.