Acalabrutinib in the treatment of chronic lymphocytic leukemia: a review of recent evidence

Chronic lymphocytic leukemia (CLL) treatment landscape has changed dramatically with the recently developed drugs targeting the B-cell receptor (BCR) signalling pathway. Acalabrutinib, a second generation Bruton tyrosine kinase inhibitor, was approved in 2020 in Russia for the treatment of patients with CLL. Acalabrutinib was developed as a more selective Bruton tyrosine kinase inhibitor then ibrutinib. This drug is aimed at reducing the adverse events that limit the use of ibrutinib, such as atrial fibrillation and bleeding. Phase I/II multicenter studies have demonstrated the efficacy and safety of acalabrutinib monotherapy in untreated CLL patients and in patients with relapsed/refractory CLL and ibrutinib intolerance. Phase III trials, ASCEND and ELEVATE-TN, compared acalabrutinib monotherapy and a combination of acalabrutinib and obinutuzumab versus standard therapies and demonstrated improved efficacy and tolerability of acalabrutinib. A phase III trial comparing acalabrutinib and ibrutinib monotherapy (ELEVATE-RR) is ongoing. The results of this study along with real-life clinical data could determine the place of acalabrutinib in CLL treatment.