Evaluating zanubrutinib for the treatment of adults with chronic lymphocytic leukemia or small lymphocytic lymphoma

ABSTRACT

Introduction

This review evaluates zanubrutinib as a treatment option for adults with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Zanubrutinib, a covalent BTK (Bruton’s tyrosine kinase) inhibitor, was recently approved by the US FDA based in part on head-to-head data demonstrating improved efficacy and safety compared to ibrutinib.

Areas covered

The review discusses the efficacy, safety, and comparative advantages of zanubrutinib, highlighting its safety profile compared to other BTK inhibitors. It also addresses the unmet needs of current therapies in CLL/SLL and provides an overview of competitor compounds and ongoing research in BTK inhibition.

Expert opinion

Zanubrutinib, the first BTK inhibitor to demonstrate superior efficacy and safety compared to another BTK inhibitor in CLL, is likely to be widely adopted due to its high-quality data and ease of use. Looking ahead, pirtobrutinib, a novel non-covalent BTK inhibitor, has shown promise in heavily pretreated CLL patients, including those unresponsive to covalent inhibitors, with ongoing phase 3 trials comparing it against ibrutinib. The field is also exploring time-limited therapies like the combination of ibrutinib and venetoclax, with ongoing trials evaluating different combinations to optimize efficacy and minimize toxicity, indicating a promising future for combination therapies in CLL treatment.

KEYWORDS:

• Chronic lymphocytic leukemia (CLL)
• small lymphocytic lymphoma (SLL)
• hematologic malignancy
• lymphoma
• zanubrutinib
• BTK inhibitors
• novel therapies

Article highlights

• Zanubrutinib’s Role in CLL/SLL Treatment: Zanubrutinib is a novel BTK inhibitor, recently approved by the US FDA, and this review examines its efficacy, safety, and comparative advantages compared to other treatments.

• Clinical Efficacy of Zanubrutinib: The review presents data from phase I, II, and III studies on zanubrutinib’s effectiveness in CLL/SLL treatment.

• Safety: Zanubrutinib demonstrates a safety profile similar to other BTK inhibitors, with respiratory infections being the most common adverse event. However, it has a lower risk of atrial fibrillation and hypertension compared to ibrutinib.

• Conclusion and Future Prospects: Zanubrutinib offers promising efficacy and improved safety in CLL/SLL treatment, with potential for combination therapies.

Declaration of interest

JR Brown has served as a consultant for Abbvie, Acerta/Astra-Zeneca, Alloplex Biotherapeutics, BeiGene, Genentech/Roche, Grifols Worldwide Operations, Hutchmed, iOnctura, Janssen, Kite, Loxo/Lilly, MEI Pharma, Merck, Numab Therapeutics, Pfizer, Pharmacyclics, and has received research funding from BeiGene, Gilead, iOnctura, Loxo/Lilly, MEI Pharma, SecuraBio, and TG Therapeutics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

JR Brown is funded by R01 CA213442/CA/NCI NIH HHS/United States. N Javidi-Sharifi is funded by 5T32HL116324-10/HL/NHLBI NIH HHS/United States.