Optimizing Ibrutinib Posology in Chronic Lymphocytic Leukemia Using a Semi-Mechanistic Pharmacometric Framework.

ABSTRACT: Ibrutinib, a Bruton's tyrosine kinase (Btk) inhibitor, is a key therapy for chronic lymphocytic leukemia (CLL). In clinical practice, adverse events, such as hypertension, frequently necessitate dose reductions or treatment discontinuation. Emerging evidence suggests that reduced doses may retain clinical efficacy while mitigating toxicity. The synergistic ibrutinib-venetoclax combination remains understudied at low doses, particularly for ibrutinib. This study aimed to explore dose optimization strategies, with/without venetoclax, in treatment-naïve (TN) and relapsed/refractory (R/R) CLL using mechanism-based, model-informed approaches to characterize the relationship between systemic ibrutinib exposure and efficacy and safety biomarkers. We leveraged data from phase 1b/2 and 3 studies, i

SUBMITTER: Ibrahim EIK 

PROVIDER: S-EPMC12706420 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature