Zanubrutinib: a new BTK inhibitor for treatment of relapsed/refractory mantle cell lymphoma.

Abstract

Mantle cell lymphoma (MCL) has historically been an aggressive disease with poor long-term survival. In the last decade, Bruton tyrosine kinase (BTK) inhibition has emerged as a new treatment strategy for MCL, especially in the relapsed/refractory (r/r) setting. Zanubrutinib, a second-generation BTK inhibitor, was approved by the U.S. Food and Drug Administration (FDA) in late 2019 for r/r MCL on the basis of combined overall response rate of 84% in a total of 118 patients from two multicenter clinical trials, BGB-3111-AU-003 and BGB-3111-206. Duration of response was 14-18 months. Although 57% of patients developed grade 3 and 4 adverse side effects including anemia, pneumonia and neutropenia, only 8% discontinued treatment suggesting zanubrutinib monotherapy was fairly well tolerated. As compared to first-generation ibrutinib, zanubrutinib has higher BTK selectivity which may result in fewer off-target effects and improved potential for combination with other targeted therapies. In addition to a confirmatory phase III trial, there are multiple ongoing studies evaluating zanubrutinib as part of two- and three-drug regimens in MCL and other B-cell malignancies. These current results and areas of further interest indicate an exciting future for zanubrutinib in the treatment of MCL.