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    2years
    Novel BTK Mutations Conferring Resistance to Non-Covalent BTK Inhibitors and Alternative Treatment Strategy (ASH 2022)
    Here,we generated and comprehensively characterized BTK and PLCG2 mutations conferring resistance to ibrutinib and five different non-covalent BTKi namely pirtobrutinib (LOXO-305), vecabrutinib (SNS-062), nemtabrutinib (ARQ-531), fenebrutinib (GDC-0853), and RN-486. We also found that cells harboring these novel BTK mutations showed differential sensitivity to the covalent vs. non-covalent BTKi. We further demonstrate the potential of venetoclax as follow up treatment upon resistance to non-covalent BTKi.
    IO biomarker
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    PLCG2 (Phospholipase C Gamma 2)
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    PLCG2 mutation • BTK mutation • BTK L845F • PLCG2 L845F
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    Venclexta (venetoclax) • Imbruvica (ibrutinib) • Jaypirca (pirtobrutinib) • vecabrutinib (SNS-062) • RN486 • fenebrutinib (RG7845) • nemtabrutinib (MK-1026)