Evaluation of Bruton's Tyrosine Kinase (BTK) inhibition with alternative doses of ibrutinib in subjects with Chronic Lymphocytic Leukemia (CLL).

• Tác giả: Sanjay Desphande, Nahor Haddish-Berhane, Aziz Ouerdani, Juan José Perez Ruixo, Emma Smith, Srimathi Srinivasan, Nicoline Treijtel, Belén Valenzuela
• Ngôn ngữ: eng
• Thông tin xuất bản: Germany : Cancer chemotherapy and pharmacology , 2025
• Bộ sưu tập: NCBI
• ID: 733597

Tóm tắt

PURPOSE: To evaluate alternative ibrutinib dosing regimens that maintain Bruton's tyrosine kinase (BTK) receptor occupancy over the entire dosing interval for CLL patients using a model-based approach. METHODS: Ibrutinib inhibits B-cell proliferation via irreversible binding of BTK. As IC RESULTS: The covalent binding model was able to describe the data and predicted that ibrutinib QD dose reduced from 420 mg to 280 mg or 140 mg may inhibit de novo synthetized BTK efficiently in a CLL population. CONCLUSION: Using a model-based approach showed that reducing the ibrutinib dosing regimen to 280 mg QD or even 140 mg in case of adverse events could maintain BTK inhibition over the entire dosing interval.