ベネトクラクスの血中濃度と副作用の関係を解明~白血病治療における最適な投与設計への道~

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2026-02-13 京都大学

京都大学医学研究科の林裕美客員研究員らは、急性骨髄性白血病(AML)治療薬ベネトクラクス(VEN)の血中濃度と副作用の関連を解析した。VENとアザシチジン併用療法を受けた152名を対象に検討した結果、VENのトラフ濃度(Ctrough)が高いほど重篤な好中球減少症など血液毒性の発症率が有意に上昇することを確認。一方、全体では血中濃度と生存率・寛解率に明確な相関はなかったが、未治療患者群では寛解率との関連が示唆された。薬物血中濃度の個体差を踏まえ、治療薬物モニタリング(TDM)に基づく個別化投与設計が、副作用を抑えつつ治療効果を維持する戦略として重要であることを示した。成果は『Scientific Reports』に掲載。

ベネトクラクスの血中濃度と副作用の関係を解明~白血病治療における最適な投与設計への道~

<関連情報>

急性骨髄性白血病の治療におけるベネトクラックストラフレベルが安全性と有効性に与える影響 Impact of venetoclax trough levels on safety and efficacy in the treatment of acute myeloid leukemia

Hiromi Hayashi,Takeo Yamagiwa,Junya Kanda,Takayuki Ishikawa,Masashi Sawa,Yasuko Miyahara,Takayoshi Tachibana,Mitsumasa Watanabe,Yasunori Ueda,Yasuhiko Tsutsumi,Kazunori Imada,Shin-ichiro Fujiwara,Tomomi Toubai,Kota Yoshifuji,Hirokazu Hirata,Hiroshi Kawabata,Masaaki Tsuji,Satoshi Wakita,Hiroki Yokoyama,Toshiyuki Kitano,Kazunori Murai,Yoshihisa Kataoka,Eri Kawata,Shun-ichi Kimura,… Akifumi Takaori-Kondo
Scientific Reports  Published:07 February 2026
DOI:https://doi.org/10.1038/s41598-026-38587-4  An unedited version of this manuscript

Abstract

Venetoclax-azacitidine chemotherapy is a key treatment for older or medically unfit patients with acute myeloid leukemia (AML). As venetoclax is metabolized via cytochrome P450 3 A, dose adjustments are required when combined with antifungal agents. However, data on venetoclax concentrations and their impact on safety and efficacy remain limited. This study analyzed the association between venetoclax trough levels and treatment outcomes in 152 AML patients (median age: 70 years). The median trough level was 1,518 ng/mL (range: 60–11,328 ng/mL), with significant interindividual variability, even after adjusting for antifungal use. High venetoclax trough levels were significantly associated with elevated creatinine and total bilirubin levels. Patients with trough levels below 1857.3 ng/mL had lower rates of hematologic toxicity during the first treatment cycle (92.9% vs. 100%, P = 0.041). In the second cycle, hematologic toxicity was lower in patients with concentrations below 1,299.3 ng/mL (68% vs. 90%, P = 0.009). In the treatment-naïve group, trough levels above 1857.3 ng/mL were associated with a higher composite complete remission rate (77.3% vs. 47.8%, P = 0.042). These findings highlight the need for venetoclax dose optimization based on drug levels to improve both safety and efficacy in AML treatment.

医療・健康
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