Acta Med. 2025, 68: 113-122
Are We Moving Toward Curative Approaches in Chronic Lymphocytic Leukemia?
, Eva Vejražková, Dominika Écsiová, Pavel Vodárek
4th Department of Internal Medicine, University Hospital Hradec Králové, Faculty of Medicine in Hradec Králové, Charles University, Hradec Králové, Czech Republic
Received January 6, 2026
Accepted January 7, 2026
Over the past decade, chronic lymphocytic leukemia (CLL) management has undergone a fundamental transformation driven by the introduction of oral targeted inhibitors. Continuous Bruton tyrosine kinase (BTK) inhibition and time-limited BCL-2–based therapy has replaced chemoimmunotherapy as the standard of care, improving survival and quality of life. Ibrutinib and its next-generation analogues, acalabrutinib and zanubrutinib, provide durable disease control with improved safety. At the same time, venetoclax combined with anti-CD20 antibodies enables deep and measurable residual disease (MRD)-negative remissions within fixed-duration regimens. Recent trials have demonstrated the feasibility of MRD-guided treatment cessation and the potential benefit of combining BTK and BCL-2 inhibition to achieve durable, chemotherapy-free responses. Ongoing research focuses on optimizing treatment sequencing, overcoming acquired resistance through non-covalent BTK inhibitors, and integrating immunotherapeutic modalities such as bispecific antibodies and CAR-T cells. The current paradigm emphasizes individualized, biomarker- and comorbidity-driven therapy based primarily on TP53 and IGHV status, with treatment selection tailored to patient fitness, tolerance, and long-term safety. This review summarizes contemporary evidence, clinical practice recommendations, and future directions in the targeted management of CLL.
Keywords
chronic lymphocytic leukemia, BTK inhibitors, BCL2 inhibitors, venetoclax, acalabrutinib, targeted therapy, comorbidities, personalized medicine.
Funding
Supported by programme COOPERATIO (research area ONCO) and DRO MH CZ (UHHK, 00179906).
References
Copyright
This is an open-access article distributed under the terms of the Creative Commons Attribution License.
