Variable Bruton Tyrosine Kinase (BTK) Resynthesis across Patients with Chronic Lymphocytic Leukemia (CLL) on Acalabrutinib Therapy Affect Target Occupancy and Reactivation of B-Cell Receptor (BCR) Signaling

In conclusion, higher target coverage was achieved when acalabrutinib was administered 100 mg BID compared with 200 mg QD. Given that BTK de novo synthesis rates do vary across patients with CLL, and that reactivation of BCR signaling correlates with lower occupancy (higher free BTK), BID dosing provides the highest target coverage for a greater number of patients.This work was supported by the Intramural Research Program of National Heart, Lung, and Blood Institute, the National Institutes of Health, and Acerta Pharma. We thank our patients for donating blood and tissue samples to make this research possible.Figure.DisclosuresCheung: Acerta Pharma: Employment, Equity Ownership; AstraZeneca: Equity Ownership. Gulrajani: Acerta Pharma: Employment, Equity Ownership. Davies-Hill: NIH/NCI: Employment. Izumi: Acerta Pharma: Employment, Equity Ownership, Patents & Royalties: Acerta Pharma, various patents for ACP-196. Covey: AstraZeneca: Equity Ownership; Acerta Pharma: Employment. Wiestner: Pharmacyclics LLC, an AbbVie Company: Research Funding.

Source: Blood - November 21, 2018 Category: Hematology Authors: Alsadhan, A. A., Cheung, J., Gulrajani, M., Cook, E. M., Pittaluga, S., Davies-Hill, T., Izumi, R., Sun, C. C., Covey, T., Wiestner, A., Herman, S. E. M. Tags: 641. CLL: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research