Bruton's tyrosine kinase inhibitors and their current status in the treatment of chronic lymphocytic leukemia
Abstract
Bruton's tyrosine kinase inhibitors (BTKi) are small molecules that interfere with the B-cell receptor signaling pathway and have an anti-tumor effect in chronic lymphocytic leukemia. Since the approval of ibrutinib in 2014, together with other targeted drugs, they have almost completely replaced standard chemotherapy regimens in relapsed disease and in the group of patients with proven TP53 aberrations are also preferred in the first-line setting.
In addition to ibrutinib, a second-generation BTKi with a lower risk of cardiac adverse events, acalabrutinib, is now available in the Czech Republic. A number of other third-generation agents are in clinical trials, of which studies with the non-covalent BTKi, pirtobrutinib, are currently ongoing in the Czech Republic too.
Combination therapy, especially with the BCL-2 inhibitor, venetoclax, offering the possibility of achieving deep, long-lasting remissions with acceptable toxicity, even in patients with prognostically unfavourable features, has also come to the fore. Unresolved issues include acquired resistance to BTKi, their impact on the immune system, and their use in patients with Richter's transformation.
This article provides an overview of the current knowledge on BTKi with an emphasis on their use in clinical practice.