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Acalabrutinib and Its Therapeutic Potential in the Treatment of Chronic Lymphocytic Leukemia: A Short Review on Emerging Data

Authors Isaac K, Mato AR

Received 4 December 2019

Accepted for publication 5 March 2020

Published 19 March 2020 Volume 2020:12 Pages 2079—2085


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Sanjeev Srivastava

Krista Isaac,1 Anthony R Mato2

1Division of Hematology and Oncology, University of Virginia Health System, Charlottesville, VA, USA; 2Chronic Lymphocytic Leukemia Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Correspondence: Krista Isaac
University of Virginia, PO Box 800716, Charlottesville, VA 22908, USA
Tel +1 215 350 8369
Fax +1 434 243 5956

Abstract: Recently, the treatment landscape for chronic lymphocytic leukemia (CLL) has changed dramatically due to the development of drugs targeting proteins in the B cell antigen receptor (BCR) pathway. Acalabrutinib, a second-generation Bruton’s tyrosine kinase (BTK) inhibitor, was recently FDA approved for treatment of treatment naïve and relapsed refractory CLL. Acalabrutinib was designed as a more selective BTK inhibitor as compared to ibrutinib in an attempt to mitigate some of the treatment limiting toxicities seen with ibrutinib such as atrial fibrillation and bleeding. In preclinical studies, acalabrutinib was demonstrated to have efficacy in CLL in both patient blood samples and murine models. A multinational phase 1/2 study demonstrated the efficacy and safety of acalabrutinib monotherapy in treatment naïve, relapsed refractory and ibrutinib-intolerant CLL patients. Subsequent phase 3 studies, ASCEND and ELEVATE-TN, compared acalabrutinib monotherapy or combination acalabrutinib and obinutuzumab to standard of care treatments and demonstrated acalabrutinib’s improved efficacy and tolerability. Currently, a phase 3 study is ongoing to compare acalabrutinib to ibrutinib monotherapy (NCT02477696). In the setting of recent FDA approval, real-world evidence will help to elucidate the optimal use of acalabrutinib in the treatment of CLL.

Keywords: acalabrutinib, BTK inhibitors, CLL, treatment naïve CLL, relapsed refractory CLL, ibrutinib toxicity

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