Association Between Venetoclax Concentration and Febrile Neutropenia in Acute Leukemia: A Retrospective Analysis

Abstract Purpose Venetoclax, a selective BCL-2 inhibitor, demonstrates efficacy in acute leukemia (AL) but variable pharmacokinetics. Therapeutic drug monitoring (TDM) serves as a critical tool for evaluating the efficacy and safety of venetoclax therapy. This study explored the factors influencing plasma venetoclax concentrations and their correlation with febrile neutropenia (FN), aiming to establish predictive thresholds. Methods AL patients receiving venetoclax between August 2023 and March 2025 were retrospectively analyzed. Plasma concentration, baseline characteristics, pharmacogenomics, and clinical parameters were collected. Univariate and multivariate linear regression analyses were performed to identify determinants of venetoclax concentration and their association with FN incidence Receiver’s operating characteristic (ROC) curve defined FN-predictive thresholds. Results Among 123 patients, median trough concentration (C 0 ) was 1409.88 ng/mL and peak concentration (C 6 ) was 2373.21 ng/mL. Multivariate analysis identified age, azoles, and transplantation status as C 0 determinants, and ABCB1 1236C>T (rs1128503) TT genotype predicted elevated C 6 . Body weight, azoles, and transplantation status independently affected C 0 /D (C0 normalized to the administered dose, D), while D-dimer (DD2) level and azoles were significant determinants of C 6 /D. Patients with venetoclax C 0 levels exceeding 1202.07 ng/mL or a C 0 /D ratio greater than 6.85 ng/mL per mg exhibited a significantly higher incidence of FN. Conclusion Higher venetoclax concentrations increase FN risk. Regular monitoring of blood venetoclax concentration using TDM can predict the risk of FN occurrence. The determination of this concentration threshold can provide a basis for optimizing the treatment quality of AL patients.