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The first-in-class Bruton tyrosine kinase (BTK), ibrutinib, demonstrated remarkable activity in chronic lymphocytic leukemia (CLL). However, its toxicity profile renders it potentially inappropriate for use in patients with bleeding or cardiovascular disorders. In response to the high demand for a safer and efficient BTK inhibitor, with improved toxicity profile, acalabrutinib as a second-generation irreversible BTK inhibitor has been approved for the treatment of CLL. This review examines the activity of acalabrutinib in treating treatment-naïve and relapsed refractory CLL and its toxicity profile when compared to ibrutinib and other drugs. It will examine the outcomes of the ELEVATE-TN, ASCEND, and ELEVATE-RR studies in detail, with a particular focus on the safety and efficacy of acalabrutinib. The strengths and weaknesses of this drug will be highlighted and future directions for research will be identified. In patients with CLL, acalabrutinib demonstrates a superior safety profile than ibrutinib and similar activity. In the first direct comparison of acalabrutinib with ibrutinib in relapsed/refractory CLL, acalabrutinib was found to demonstrate non-inferior progression-free survival, with fewer cardiovascular adverse events.

Acalabrutinib: a bruton tyrosine kinase inhibitor for the treatment of chronic lymphocytic leukemia