Onkológia 2/2023

Acalabrutinib, a new Bruton's tyrosine kinase inhibitor in first line CLL treatment

Although CLL remains an incurable disease, more and more treatment options are bringing clinical benefits to patients with longer duration of response and less toxicity commonly seen with conventional chemotherapeutics. The treatment of CLL, which has gone through various stages from chemotherapy to chemoimmunotherapy (CIT) to the current targeted therapy, reflects one of the great achievements in current medicine. The access of targeted drugs, along with the development of monoclonal antibodies, has enabled CLL patients to achieve deeper remissions and changed current therapeutic approaches and treatment goals, leading to significant improvements in the quality and length of life of CLL patients. Different treatment strategies are available for the first-line treatment of CLL. Various biological and genetic markers have their prognostic value. Del (17p), TP53 mutation, as well as unmutated IGHV predict aggressive disease course, resistance to CIT, and shorter time to progression. These patients should be indicated for first-line treatment for continuous treatment with Bruton's tyrosine kinase (BTK) inhibitors acalabrutinib or ibrutinib until disease progression or fix-duration treatment with a combination of venetoclax and obinutuzumab. The choice of treatment depends, beyond of the mentioned risk factors, on age, performance status, comorbidities, chronic medication, preference, gene profile. Bruton's tyrosine kinase is an essential kinase in the B cell receptor (BCR) signaling pathway and a driver of CLL and other B cell malignancies. The first BTK inhibitor, ibrutinib, is used to treat CLL, mantle cell lymphoma, and Waldenström's macroglobulinemia. However, it has adverse effects such as bleeding, rash, and atrial fibrillation. The reason for the increased incidence of cardiovascular adverse events with ibrutinib treatment is not clear, but it may be related to the fact that ibrutinib at low concentrations also irreversibly binds to Src kinase and several other kinases. Therefore, more selective BTK inhibitors were investigated. Acalabrutinib, a new second-generation irreversible BTK inhibitor, has been shown to be more effective and selective for BTK kinase than ibrutinib. It significantly improved progression-free survival compared to CIT, providing a chemotherapy-free treatment option with an acceptable side-effect profile. Acalabrutinib represents a new treatment option in Slovakia for patients with previously untreated symptomatic CLL.

Keywords: acalabrutinib, chronic lymphocytic leukemia, Bruton‘s tyrosine kinase