Mechanisms of Resistance to Noncovalent Bruton's Tyrosine Kinase Inhibitors.
Eric WangXiaoli MiMeghan C ThompsonSkye MontoyaRyan Q NottiJumana AfaghaniBenjamin H DurhamAlex PensonMatthew T WitkowskiSydney X LuJessie BourcierSimon J HoggCaroline EricksonDan CuiHana ChoMichael SingerTulasigeri M TotigerSana ChaudhryMark GeyerAlvaro J AlencarAdam J LinleyM Lia PalombaCatherine C CoombsJae H ParkAndrew ZelenetzLindsey Elizabeth RoekerMary RosendahlDonald E TsaiKevin EbataBarbara BrandhuberDavid M HymanIannis AifantisAnthony MatoJustin TaylorOmar Abdel-WahabPublished in: The New England journal of medicine (2022)
Resistance to noncovalent BTK inhibitors arose through on-target BTK mutations and downstream PLCγ2 mutations that allowed escape from BTK inhibition. A proportion of these mutations also conferred resistance across clinically approved covalent BTK inhibitors. These data suggested new mechanisms of genomic escape from established covalent and novel noncovalent BTK inhibitors. (Funded by the American Society of Hematology and others.).