Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

The Role of Bruton’s Kinase Inhibitors in Chronic Lymphocytic Leukemia: Current Status and Future Directions

Version 1 : Received: 15 December 2021 / Approved: 16 December 2021 / Online: 16 December 2021 (16:13:54 CET)

How to cite: Robak, T.; Witkowska, M.; Smolewski, P. The Role of Bruton’s Kinase Inhibitors in Chronic Lymphocytic Leukemia: Current Status and Future Directions. Preprints 2021, 2021120282 (doi: 10.20944/preprints202112.0282.v1). Robak, T.; Witkowska, M.; Smolewski, P. The Role of Bruton’s Kinase Inhibitors in Chronic Lymphocytic Leukemia: Current Status and Future Directions. Preprints 2021, 2021120282 (doi: 10.20944/preprints202112.0282.v1).

Abstract

The use of the Bruton’s tyrosine kinase (BTK) inhibitors has changed the management and clinical history of patients with chronic lymphocytic leukemia (CLL). BTK is a critical molecule that interconnects B-cell antigen receptor (BCR) signaling. BTKIs are classified into two categories: irreversible (covalent) inhibitors and reversible (non-covalent) inhibitors. Ibrutinib is the first irreversible BTK inhibitor approved by the U.S. Food and Drug Administration in 2013 as a breakthrough therapy in CLL patients. Subsequently, several studies evaluated the efficacy and safety of new agents with reduced toxicity when compared with ibrutinib. Two other irreversible, second-generation BTK inhibitors, acalabrutinib and zanubrutinib, were developed to reduce ibrutinib-mediated adverse effects. Additionally, new reversible BTK inhibitors are currently under development in an early phase studies to improve their activity and to diminish adverse effects. This review summarizes the pharmacology, clinical efficacy, safety, dosing, drug-drug interactions associated with the treatment of CLL with BTK inhibitors, and examines its further implications.

Keywords

Acalabrutinib; Bruton’s tyrosine kinase; BTK; CLL; Covalent inhibitors; COVID-19; Ibrutinib; Non-covalent inhibitors; Fenebrutinib; MK1026; Pirtobrutinib; Spebrutinib; Tirabrutinib; Zanubrutinib

Subject

MEDICINE & PHARMACOLOGY, Oncology & Oncogenics

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