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Purpose <p>Venetoclax, a selective BCL-2 inhibitor, demonstrates efficacy in acute leukemia (AL) but variable pharmacokinetics. Therapeutic drug monitoring (TDM) may provide valuable pharmacologic insights for optimizing venetoclax therapy. This study explored the factors influencing plasma venetoclax concentrations and their correlation with febrile neutropenia (FN), aiming to establish predictive thresholds.</p> Methods <p>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 concentrations and factors associated with FN incidence. Receiver operating characteristic (ROC) curves were used to define FN-predictive thresholds.</p> Results <p>The cohort comprised 123 patients, with FN developing in 35 cases (28.5%). The median trough concentration (C<sub>0</sub>) and peak concentration (C<sub>6</sub>) were significantly higher in the FN group compared to non-FN patients (1519.55 ng/mL vs. 1400.32 ng/mL and 2834.50 ng/mL vs. 2337.74 ng/mL, respectively). Multivariate analysis identified age, azoles, and prior transplantation as C<sub>0</sub> determinants, and <i>ABCB1 1236&#xa0;C&gt; T (rs1128503) TT</i> genotype predicted elevated C<sub>6</sub>. Patients with venetoclax C<sub>0</sub> levels exceeding 1202.07 ng/mL or a C<sub>0</sub>/D ratio greater than 6.85 ng/mL per mg exhibited a significantly higher incidence of FN. Higher C<sub>6</sub>/D levels significantly correlated with increased FN incidence in the patients with venetoclax and hypomethylating drugs (Ven-HMA).</p> Conclusion <p>Higher venetoclax concentrations increase FN risk. Regular monitoring of blood venetoclax concentration using TDM may help identify patients at increased FN risk. The determination of this concentration threshold can provide a basis for optimizing the treatment quality of AL patients.</p>

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Association between venetoclax concentration and febrile neutropenia in acute leukemia: a retrospective analysis

  • 期刊论文

  • 发表日期：

    2026年8月1日

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  • Yuting Yan,
  • Jin Sun,
  • Yujiao Guo,
  • Jieyu Sun,
  • Yu Zhu,
  • Luning Sun,
  • Yongqing Wang

摘要

Purpose

Venetoclax, a selective BCL-2 inhibitor, demonstrates efficacy in acute leukemia (AL) but variable pharmacokinetics. Therapeutic drug monitoring (TDM) may provide valuable pharmacologic insights for optimizing 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 concentrations and factors associated with FN incidence. Receiver operating characteristic (ROC) curves were used to define FN-predictive thresholds.

Results

The cohort comprised 123 patients, with FN developing in 35 cases (28.5%). The median trough concentration (C0) and peak concentration (C6) were significantly higher in the FN group compared to non-FN patients (1519.55 ng/mL vs. 1400.32 ng/mL and 2834.50 ng/mL vs. 2337.74 ng/mL, respectively). Multivariate analysis identified age, azoles, and prior transplantation as C0 determinants, and ABCB1 1236 C> T (rs1128503) TT genotype predicted elevated C6. Patients with venetoclax C0 levels exceeding 1202.07 ng/mL or a C0/D ratio greater than 6.85 ng/mL per mg exhibited a significantly higher incidence of FN. Higher C6/D levels significantly correlated with increased FN incidence in the patients with venetoclax and hypomethylating drugs (Ven-HMA).

Conclusion

Higher venetoclax concentrations increase FN risk. Regular monitoring of blood venetoclax concentration using TDM may help identify patients at increased FN risk. The determination of this concentration threshold can provide a basis for optimizing the treatment quality of AL patients.