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Resistance Mechanisms for the Bruton's Tyrosine Kinase Inhibitor Ibrutinib

2014; Massachusetts Medical Society; Volume: 370; Issue: 24 Linguagem: Inglês

10.1056/nejmoa1400029

1533-4406

Jennifer A. Woyach, Richard R. Furman, Ta-Ming Liu, Hatice Gülçin Özer, Marc Zapatka, Amy S. Ruppert, Ling Xue, Daniel Hsieh-Hsin Li, Susanne Steggerda, Matthias Versele, Sandeep S. Davé, Jenny Zhang, Ayse Selen Yilmaz, Samantha Jaglowski, Kristie A. Blum, Arletta Lozanski, Gerard Lozanski, Danelle F. James, Jacqueline C. Barrientos, Peter Lichter, Stephan Stilgenbauer, Joseph J. Buggy, Betty Chang, Amy J. Johnson, John C. Byrd,

Lymphoma Diagnosis and Treatment

Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (BTK) and is effective in chronic lymphocytic leukemia (CLL). Resistance to irreversible kinase inhibitors and resistance associated with BTK inhibition have not been characterized. Although only a small proportion of patients have had a relapse during ibrutinib therapy, an understanding of resistance mechanisms is important. We evaluated patients with relapsed disease to identify mutations that may mediate ibrutinib resistance.