OBJECTIVE To evaluate clinical value of three Bruton tyrosine kinase inhibitors(BTKi) in the treatment of chronic lymphocytic leukemia(CLL) using a rapid health technology assessment(rHTA).

METHODS Systematic retrieval was performed from databases including PubMed, Embase, and the Cochrane Library, as well as relevant websites and databases of health technology assessment(HTA) agencies to select eligible studies. Then, literature screening, quality assessment, data extraction and analysis were performed independently by two reviewers. Meanwhile, semi-structured interviews and closed-ended questionnaires were conducted to obtain experts’ suggestions and opinions. Finally, integrating the literature derived evidence and expert recommendations obtained from surveys, all evidence was synthesized and results were presented across six dimensions: efficacy, safety, economy, innovation, suitability, and accessibility.

RESULTS A total of 40 studies were included, including 17 systematic reviews/meta-analyses, 13 economics studies, and 10 HTA reports. In terms of efficacy, the progression-free survival(PFS) and overall survival(OS) of BTKi were significantly longer than chemotherapy, immunotherapy, and chemoimmunotherapy. Zanubrutinib and acalabrutinib could further prolong the PFS of CLL patients. In terms of safety, BTKi were well tolerated, but hypertension, bleeding events, and cardiotoxicity were more likely to be observed. According to the HTA reports and economics studies, zanubrutinib showed a lower total drug cost and potentially offered a greater cost-effectiveness advantage compared to ibrutinib. As oral agents with a novel mechanism of action, BTKi were considered by most experts to be superior to chemoimmunotherapy regimens in terms of applicability. According to the accessibility scores assessed by experts, zanubrutinib achieved the highest score among the three BTKi.

CONCLUSION Based on the existing limited evidence, three BTKi are recommended for the treatment of CLL in China. Among the three BTKi, zanubrutinib is more economical, safe, and accessible in China, and may be of greater clinical value for CLL patients.