Novel mechanisms of resistance in CLL: variant BTK mutations in second-generation and noncovalent BTK inhibitors
- Author(s)
- Tam, CS; Balendran, S; Blombery, P;
- Details
- Publication Year 2025-03-06,Volume 145,Issue #10,Page 1005-1009
- Journal Title
- Blood
- Publication Type
- Review
- Abstract
- Bruton tyrosine kinase inhibitors (BTKis) are an established standard of care in chronic lymphocytic leukemia. The covalent BTKis ibrutinib, acalabrutinib, and zanubrutinib bind to BTK C481 and are all susceptible to the C481S mutation. Noncovalent BTKi, including pirtobrutinib, overcome C481S resistance but are associated with multiple variant (non-C481) BTK mutations, including those associated with resistance to acalabrutinib and zanubrutinib (T474 codon and L528W mutations). We review the current knowledge on variant BTK mutations, discuss their clinical implications, and consider their impact on clinical trials.
- Publisher
- American Society of Hematology
- Keywords
- Humans; *Agammaglobulinaemia Tyrosine Kinase/genetics/antagonists & inhibitors; *Leukemia, Lymphocytic, Chronic, B-Cell/genetics/drug therapy; *Drug Resistance, Neoplasm/genetics; *Protein Kinase Inhibitors/therapeutic use; *Mutation; Pyrimidines/therapeutic use; Pyrazoles/therapeutic use; Piperidines/therapeutic use; Adenine/analogs & derivatives; Benzamides; Pyrazines
- Department(s)
- Pathology
- Publisher's Version
- https://doi.org/10.1182/blood.2024026672
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-04-10 01:21:58
Last Modified: 2025-04-10 01:22:30