Review Articles
Vol. 17 No. 1 (2025): Review Articles, Original Article, Scientific Letter, Case Reports Letter to the Editor
BRUTON’S TYROSINE KINASE (BTK) MUTATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): A CLINICAL VIEW.
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Received: May 19, 2025
Accepted: May 31, 2025
Accepted: May 31, 2025
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Bruton’s tyrosine kinase inhibitors (BTKis) have reshaped the management of chronic lymphocytic leukemia (CLL). The first-generation BTKi ibrutinib demonstrated significant efficacy, leading to the development of second-generation agents (acalabrutinib, zanubrutinib) with improved selectivity and safety. However, resistance—most often driven by BTK C481S mutations—remains a major therapeutic limitation.
Non-covalent BTKis, such as pirtobrutinib, offer effective options for patients relapsing after covalent BTKi therapy. However, the emergence of novel resistance mutations continues to limit durable responses. As insights into the molecular basis of BTK resistance evolve, routine mutation testing is poised to become integral to personalized treatment in CLL. Future clinical trials are expected to adopt mutation-driven stratification to guide therapeutic sequencing. Ultimately, overcoming BTKi resistance will require innovative strategies, including BTK degraders, bispecific antibodies, and T cell–engaging immunotherapies.
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“BRUTON’S TYROSINE KINASE (BTK) MUTATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): A CLINICAL VIEW”. (2025) Mediterranean Journal of Hematology and Infectious Diseases, 17(1), p. e2025053. doi:10.4084/MJHID.2025.053.
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