REVIEW article
Oncol. Rev.
Sec. Oncology Reviews: Reviews
LIGHTS AND SHADES OF FRONT-LINE TREATMENT WITH COVALENT BTK INHIBITORS COMBINED WITH VENETOCLAX IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA
Provisionally accepted
- 1University of Padua, Padua, Italy
- 2Universita degli Studi di Roma La Sapienza, Rome, Italy
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This review focused on trials investigating the front-line covalent BTK inhibitors (cBTKi) and venetoclax (V) combination administered in a fixed-duration (CAPTIVATE, GLOW, AMPLIFY trials) or minimal residual disease (MRD)-guided manner (MDACC, FLAIR, ERADIC, HOVON NEXT STEP, SEQUOIA arm D trials) in patients with chronic lymphocytic leukemia (CLL). We reviewed data from these studies to highlight their therapeutic activity and toxicity profile. Despite the heterogeneity in patients' characteristics, treatment schedule, and duration, most patients achieved deep responses with undetectable MRD and prolonged progression-free survival (PFS) with BTKi+V regimens. MRD-guided treatments yielded higher PFS rates, including patients with high-risk genetic characteristics, such as those with unmutated IGHV and TP53 disruption. The cBTKi+V regimen is easy to manage and relatively well tolerated. However, cBTKi-related cardiovascular toxicities remain a limiting concern, especially for the use of cBTKi+V in some older patients.
Keywords: acalabrutinib, chronic lymphocytic leukemia, fixed duration therapy, Ibrutinib, venetoclax, zanubrutinib
Received: 11 Sep 2025; Accepted: 30 Nov 2025.
Copyright: © 2025 VISENTIN and Mauro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: ANDREA VISENTIN
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