Assessing the pharmacokinetics of acalabrutinib in the treatment of chronic lymphocytic leukemia

ABSTRACT

Introduction

The first-in-class BTK inhibitor ibrutinib has substantially changed the therapeutic landscape of chronic lymphocytic leukemia (CLL). The next-generation BTK inhibitor acalabrutinib is more selective and may have less off-target toxicities as compared to ibrutinib. Acalabrutinib has demonstrated safety and efficacy in CLL and has been approved to treat CLL.

Areas covered

Current clinical trials investigated acalabrutinib monotherapy or acalabrutinib-based combination therapies in relapsed/refractory and treatment-naive CLL. Data on the efficacy and safety of acalabrutinib in clinical trials were summarized in this review. The pharmacokinetic and pharmacodynamic data of acalabrutinib were also discussed.

Expert opinion

Acalabrutinib selectively inhibits BTK by covalent binding and shows rapid absorption and elimination. Acalabrutinib does not inhibit EGFR, TEC, or ITK and shows fewer off-target toxicities. Completed phase 3 trials have demonstrated that acalabrutinib improves the outcomes of patients with relapsed/refractory CLL and patients with treatment-naive CLL. The phase 3 trial that evaluates acalabrutinib versus ibrutinib has met its primary endpoint. Early phase studies suggested the combinations of acalabrutinib with a CD20 antibody and venetoclax led to high rates of undetectable minimal residual disease in the bone marrow in CLL patients and might provide a fixed-duration therapeutic option for patients with CLL.

KEYWORDS:

• Acalabrutinib
• chronic lymphocytic leukemia
• bruton’s tyrosine kinase
• inhibitor
• pharmacokinetics

Declaration of interest

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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Box 1. Drug summary box

Table

Reviewer Disclosures

One of the peer reviewers on this manuscript has received research funding from AstraZeneca and Pharmacyclics. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

The study was supported by the National Natural Science Foundation of China (Grant No.81720108002), National Major Science and Technology Projects of China (Grant No.2018ZX09734007), and Jiangsu Provincial Special Program of Medical Science (BE2017751).