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

• Published in: Journal of hematology and oncology Vol. 13; no. 1; pp. 48 - 12
• Main Authors: Xu, Wei, Yang, Shenmiao, Zhou, Keshu, Pan, Ling, Li, Zengjun, Zhou, Jianfeng, Gao, Sujun, Zhou, Daobin, Hu, Jianda, Feng, Ru, Huang, Haiwen, Ji, Meng, Guo, Haiyi, Huang, Jane, Novotny, William, Feng, Shibao, Li, Jianyong
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11.05.2020; BioMed Central; BMC
• Subjects: Adult; Agammaglobulinaemia Tyrosine Kinase - antagonists & inhibitors; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Bronchopulmonary infection; Bruton's tyrosine kinase; Cardiac arrhythmia; Cell activation; Cell adhesion & migration; China - epidemiology; Chronic lymphocytic leukemia; Clinical medicine; Clinical trial; Clinical trials; Confidence intervals; Consent; Deoxyribonucleic acid; DNA; Drug therapy; Female; Growth factors; Health aspects; Hematology; Hepatitis; Humans; Ibrutinib; Idelalisib; Infections; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - epidemiology; Lymphatic leukemia; Lymphocytosis; Lymphoma; Lymphomas; Male; Medical research; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - epidemiology; Neutropenia; Oncology; Piperidines - adverse effects; Piperidines - therapeutic use; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Protein-tyrosine kinase; Pyrazoles - adverse effects; Pyrazoles - therapeutic use; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Receptor mechanisms; Relapsed/refractory; Respiratory tract diseases; Studies; Thrombocytopenia; Treatment Outcome; Tyrosine; Venetoclax; Zanubrutinib; China; Bruton’s tyrosine kinase; Clinical trial; Chronic lymphocytic leukemia; Relapsed/refractory; Zanubrutinib
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-020-00884-4

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 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.