Treatment of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with the BTK inhibitor zanubrutinib: phase 2, single-arm, multicenter study

Wei Xu, Shenmiao Yang, Keshu Zhou, Ling Pan, Zengjun Li, Jianfeng Zhou, Sujun Gao, Daobin Zhou, Jianda Hu, Ru Feng, Haiwen Huang, Meng Ji (+5 others)
2020 Journal of Hematology & Oncology  
Bruton tyrosine kinase (BTK) inhibitors have demonstrated a high degree of efficacy in the treatment of B cell malignancies characterized by constitutive B cell receptor activation, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The efficacy and safety of zanubrutinib, an investigational highly selective BTK inhibitor, was evaluated in this single-arm, phase 2 study of Chinese patients with relapsed/refractory CLL/SLL. The primary endpoint was overall response rate
more » ... as assessed by an independent review committee. Of the 91 evaluable patients, 77 (84.6%) achieved a response, with three (3.3%), 54 (59.3%), and 20 (22%) patients achieving a complete response, partial response, and partial response with lymphocytosis, respectively, after a median follow-up of 15.1 months. The estimated 12-month event-free rate for duration of response was 92.9%. The most commonly reported grade ≥ 3 adverse events (AEs) were neutropenia (44%), thrombocytopenia (15.4%), lung infection/pneumonia (13.2%), upper respiratory tract infection (9.9%), and anemia (8.8%). The 12-month overall survival rate was 96%. Eight (9.0%) patients discontinued zanubrutinib due to AEs, and seven (8.0%) patients required at least one dose reduction. Treatment of patients with relapsed/refractory CLL/SLL with zanubrutinib was generally well tolerated and resulted in a high overall response rate, thereby conferring a favorable benefit-risk profile. Prospectively registered in China public registry (CTR20160890) on December 7, 2016: http://www.chinadrugtrials.org.cn/. Retrospectively registered in ClinicalTrials.gov (NCT03206918) on July 2, 2017.
doi:10.1186/s13045-020-00884-4 pmid:32393328 fatcat:4hm7gqsc4bgr7kyej7p2aympnu