Yu‐Ting Yan, Jin Sun, Yujiao Guo, Jieyu Sun, Yu Zhu, Luning Sun, Yongqing Wang
Background 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 identified the determinants of venetoclax exposure and their association with FN incidence. Receiver’s operating characteristic (ROC) curve defined FN-predictive thresholds. Results Among 123 patients, median C0 was 1442.25 ng/mL and C5.5 was 2373.21 ng/mL. Multivariate analysis identified age, azoles, and transplantation status as C0 determinants, and ABCB1 rs1128503 AA genotype predicted elevated C5.5. Body weight, azoles, and transplantation status independently affected C0/D, while D-dimer (DD2) level and azoles were significant determinants of C5.5/D. Patients with venetoclax C0 levels exceeding 1202.065 ng/mL or a C0/D ratio greater than 6.8482 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.