Drug Evaluation

Acalabrutinib and its use in treatment of chronic lymphocytic leukemia

Yasir Khan

*Author for correspondence:

E-mail Address: yasirk@uci.edu

UCI Medical Center, Orange, CA 92868, USA

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Susan O'Brien

UCI Medical Center, Orange, CA 92868, USA

Chao Family Comprehensive Cancer Center, Orange, CA 92868, USA

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Published Online:1 Nov 2018https://doi.org/10.2217/fon-2018-0637

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Abstract

Acalabrutinib received an accelerated US FDA approval for patients with relapsed/refractory mantle cell lymphoma in 2017 and is currently being evaluated in chronic lymphocytic leukemia (CLL). To date, ibrutinib is the only Bruton tyrosine kinase (BTK) inhibitor that's approved for treatment of CLL. Acalabrutinib is a second generation BTK inhibitor that binds covalently to the Cys481 residue on BTK and has half maximal inhibitory concentration (IC₅₀) of 3 nM. In preclinical mouse models, acalabrutinib significantly reduced proliferation of CLL cells. Results of Phase I/II trials revealed overall response rates (ORR) of 96% in treatment-naive, 93% in relapsed/refractory and 76% in ibrutinib intolerant patients with CLL. The most common adverse effects (>20%) were grade 1–2 comprising constitutional symptoms, GI toxicity, rash and myelosuppression. There were limited grade 3 or 4 toxicities, involving syncope, pneumonia, hypertension, atrial fibrillation, neutropenia and thrombocytopenia.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 15, No. 6

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History

Received 21 August 2018

Accepted 10 October 2018

Published online 1 November 2018

Published in print February 2019

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Keywords

Author contributions

Y Khan was responsible for conducting literature search and writing of the manuscript. S O'Brien supervised literature search and helped with editing and writing of the manuscript.

Financial & competing interest disclosure

S O'Brien is a consultant for Amgen, Astellas, Celgene, GlaxoSmithKline, Janssen Oncology, Aptose Bioscience Inc., Vaniam Group LLC, AbbVie, Alexion, Gilead, Pharmacyclics, TG Therapeutics, Pfizer and Sunesis. S O'Brien has research support for Kite, Regeneron, Acerta, Gilead, Pharmacyclics, TG Therapeutics, Pfizer, Sunesis. 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.

No writing assistance was utilized in the production of this manuscript.

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