An evaluation of zanubrutinib, a BTK inhibitor, for the treatment of chronic lymphocytic leukemia

Abstract

Introduction: Recent years have seen a tremendous increase in the availability of therapeutic options for the management of patients with chronic lymphocytic leukemia (CLL). Notable among those are Bruton's tyrosine kinase (BTK) and b-cell lymphoma-2 (bcl-2) inhibitors.

Areas covered: The authors provide a brief overview of the BTK signaling pathway as well as available, approved BTK inhibitors for CLL. In addition, they review pre-clinical and clinical data related to zanubrutinib and its use and CLL and other lymphoid malignancies.

Expert opinion: Two BTK inhibitors are currently Food and Drug Administration (FDA) approved for use in CLL, and multiple additional agents are in development. Zanubrutinib is currently approved for the treatment of patients with relapsed mantle cell lymphoma and has demonstrated an impressive safety and efficacy profile. The choice of a specific BTK inhibitor for clinical use is dependent on its efficacy and relative toxicity profile. In addition, drug interactions also influence this decision. Zanubrutinib therefore provides an exciting option to utilize a specific BTK inhibitor with potentially limited toxicities. Additional comparative studies are currently underway to establish its advantage over currently available BTK inhibitors. Combination strategies are also being pursued to increase the depth and durability of remissions.

Keywords: Bruton’s tyrosine kinase inhibitor (BTKi); Zanubrutinib; chronic lymphocytic leukemia (CLL); non-Hodgkin lymphoma (NHL); small lymphocytic lymphoma (SLL).