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ASH 2023 | Acquired mutations associated with resistance to BTKi in patients with CLL

Stephan Stilgenbauer, MD, University of Ulm, Ulm, Germany, discusses acquired mutations that underlie resistance to BTK inhibitors (BTKi) in patients with chronic lymphocytic leukemia (CLL). Mutations arising at position C481 of BTK can cause resistance to covalent BTKi like ibrutinib, acalabrutinib, and zanubrutinib. Resistance to the non-covalent BTKi pirtobrutinib could lead to resistance against subsequent covalent inhibitors, emphasizing the crucial need for optimal sequencing strategies, although the non-covalent BTKi nemtabrutinib overcomes this. This interview took place at the 65th ASH Annual Meeting and Exposition, held in San Diego, CA.

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Consultancy: Amgen, Abbvie, Celgene, Gilead, GSK, Roche, Janssen, Novartis, Sunesis, AstraZeneca; Honoraria: Amgen, Abbvie, Celgene, Gilead, GSK, Roche, Janssen, Novartis, Sunesis, AstraZeneca; Travel support: Amgen, Abbvie, Celgene, Gilead, GSK, Roche, Janssen, Novartis, Sunesis, AstraZeneca; Research Funding: Amgen, Abbvie, Celgene, Gilead, GSK, Roche, Janssen, Novartis, Sunesis, AstraZeneca.