Acalabrutinib: a highly selective, potent Bruton tyrosine kinase inhibitor for the treatment of chronic lymphocytic leukemia

Abstract

Inhibiting the activity of Bruton tyrosine kinase (BTK) prevents the activation of the B‐cell receptor (BCR) signaling pathway, which in turn prevents both B‐cell activation and BTK‐mediated activation of downstream survival pathways. Acalabrutinib is an orally available, highly selective, next-generation inhibitor of BTK. Based on the results of two key phase 3 trials (ELEVATE-TN in patients with previously untreated chronic lymphocytic leukemia [CLL] and ASCEND in patients with relapsed or refractory CLL), which demonstrated superior progression-free survival while maintaining favorable tolerability, acalabrutinib was granted US Food and Drug Administration (FDA) approval in 2019 for the treatment of patients with CLL. Acalabrutinib appears to offer similar efficacy but a significantly improved tolerability profile to first-generation agents. Acalabrutinib is a good candidate to combine with other anti-cancer therapies, including B-cell lymphoma 2 inhibitors and monoclonal antibodies, a factor that may help to further improve clinical outcomes in CLL.

Keywords:

• Acalabrutinib
• BTK inhibitor
• chronic lymphocytic leukemia

Disclosure statement

PG received honoraria from AbbVie, Acerta/AstraZeneca, Adaptive, ArQule, BeiGene, CelGene/Juno, Gilead, Janssen, Lilly and Sunesis, and research funding from AbbVie, Gilead, Janssen and Sunesis. MD-D and WJ received research grants from Janssen, AstraZeneca and BeiGene. LS received honoraria from AbbVie, AstraZeneca, Gilead and Janssen. No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors would like to thank Zoe Kelly, PhD (Oxford PharmaGenesis, Cambridge, UK) who provided medical writing support, funded by AstraZeneca.