Conference Proceedings
BTK Leu528Trp-a Potential Secondary Resistance Mechanism Specific for Patients with Chronic Lymphocytic Leukemia Treated with the Next Generation BTK Inhibitor Zanubrutinib
Sasanka M Handunnetti, Chloe Pek Sang Tang, Nguyen Tamia, Xing Zhou, Ella Thompson, Hanzi Sun, Haimei Xing, Bo Zhang, Yin Guo, Lesley Ann Sutton, Paolo Ghia, Richard Rosenquist, Lydia Scarfo, Silvia Bonfiglio, John F Seymour, Mary Ann Anderson, Andrew W Roberts, David CS Huang, Ye Liu, Chan Y Cheah Show all
BLOOD | AMER SOC HEMATOLOGY | Published : 2019
Abstract
One of the most common secondary resistance mechanisms to ibrutinib (IBR, a first-generation, irreversible Bruton's tyrosine kinase [BTK] inhibitor) in CLL is the development of mutations in BTK involving Cys481, leading to impaired drug binding (Woyach et al, NEJM 2014; Furman et al, NEJM 2014). The mechanisms of resistance to second generation BTK inhibitors are currently unknown. We aimed to assess the spectrum of acquired BTK mutations in patients with CLL progression on zanubrutinib (ZANU), a second-generation, irreversible inhibitor of BTK. We identified 38 CLL patients, treated with ZANU on clinical trials (NCT02343120, NCT02569476, NCT03336333, NCT02795182) at three ce..
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