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Review
. 2024 Apr;20(4):207-224.
doi: 10.1080/17425255.2024.2334322. Epub 2024 Mar 25.

Metabolic and toxicological considerations of Bruton's tyrosine kinase inhibitors for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma

Anna Wolska-Washer  1   2 , Paweł Robak  1   2 , Magdalena Witkowska  1   2 , Tadeusz Robak  1   3
Affiliations
Review

Metabolic and toxicological considerations of Bruton's tyrosine kinase inhibitors for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma

Anna Wolska-Washer et al. Expert Opin Drug Metab Toxicol. 2024 Apr.

Abstract

Introduction: Bruton tyrosine kinase inhibitors (BTKi) have been used for the management of human diseases since the approval of the first-in class agent, ibrutinib, by the Food and Drug Administration in 2013 for the treatment of patients with mantle cell lymphoma (MCL). Ibrutinib is a covalent inhibitor along with second-class BTKis: acalabrutinib and zanubrutinib. These well-tolerated agents have transformed the treatment landscape of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). A new class of these inhibitors, non-covalent, might become an answer to the emerging resistance by avoiding the sustained contact with the kinase binding domain.

Areas covered: This article examines the chemical composition, mechanism of action, metabolic characteristics, and potential toxicity of inhibitors targeting Bruton tyrosine kinase. A comprehensive search was conducted across English-language articles in PubMed, Web of Science, and Google Scholar.

Expert opinion: Bruton tyrosine kinase inhibitors have greatly enhanced the armamentarium against lymphoid malignancies including CLL/SLL. Their future lies in the choice of appropriate patients who will benefit from the treatment without significant adverse reaction. Combination chemotherapy-free fixed-duration regimens with targeted molecules will allow for MRD-driven approach in patients with CLL/SLL in the near future.

Keywords: Acalabrutinib; Bruton tyrosine kinase inhibitor; cardiotoxicity; chronic lymphocytic leukemia; ibrutinib; pirtobrutinib; zanubrutinib.

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