incrementalNew research
Genomics-guided treatment selection advances in WM
Waldenström's Macroglobulinemia →Summary
Treon et al. (Blood 2024) published a comprehensive genomics-guided approach to BTK inhibitor selection in WM. MYD88 and CXCR4 genotyping now informs first-line treatment choice. MYD88 wild-type patients (~5-10%) respond poorly to ibrutinib and may benefit from alternative approaches such as chemoimmunotherapy or venetoclax-based regimens.
Related treatments
Related genes
MYD88L265P (somatic)
Defining molecular hallmark of WM. Gain-of-function mutation causing constitutive Myddosome assembly, BTK activation, and NF-kB-driven B-cell survival. Discovered by Treon et al. 2012 via whole-genome sequencing.CXCR4WHIM-like mutations (most commonly S338X)
Second most common somatic event in WM. Over 40 different mutations described, both nonsense and frameshift. Mutations cause sustained CXCR4 signaling and enhanced bone marrow homing via CXCL12.More from Waldenström's Macroglobulinemia
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incrementalNew research
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significantTreatment update
Pirtobrutinib shows activity in covalent BTK inhibitor-pretreated WM
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Ibrutinib + venetoclax fixed-duration combination in treatment-naive WM
ID: waldenstroms-macroglobulinemia-update-4Type: new_researchImpact: incremental