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Purpose <p>The effects of polymorphisms in <i>CYP3A4</i>, <i>UGT2B7</i>, <i>ABCB1</i>, <i>ABCG2</i>, <i>ABCC2</i>, <i>NR1I2</i>, and <i>AHR</i> genes on asciminib exposure were evaluated in Japanese patients with chronic myeloid leukemia.</p> Methods <p>Plasma concentrations of asciminib (40&#xa0;mg twice daily [BID] or 80&#xa0;mg once daily [QD]) were measured by high-performance liquid chromatography. Statistical analysis was performed using SPSS (<i>P</i> &lt; 0.05).</p> Results <p>For both regimens, the median asciminib area under the concentration–time curve (AUC) was significantly higher in female than in male patients (<i>P</i> = 0.009 and 0.004, respectively). Significant correlations were observed between the asciminib AUC of 40&#xa0;mg BID or 80&#xa0;mg QD and body weight (<i>P</i> = 0.042 and &lt; 0.001, respectively). The asciminib AUC<sub>0-12</sub> of 40&#xa0;mg BID in patients with the -25385&#xa0;T allele of the <i>NR1I2</i> -25385C &gt; T polymorphism was significantly lower than that in patients with the -25385C/C genotype (5363 and 10607&#xa0;ng∙h/mL, respectively, <i>P</i> = 0.001). In multiple regression analyses, the <i>NR1I2</i> -25385C &gt; T polymorphism (<i>P</i> = 0.001) and female sex (<i>P</i> = 0.002) were independently predictive of a higher asciminib AUC<sub>0-12</sub> for the 40&#xa0;mg BID regimen (determination coefficient: 52.8%), whereas body weight (<i>P</i> &lt; 0.001) and female sex (<i>P</i> = 0.047) were independently predictive of a higher asciminib AUC<sub>0-24</sub> for the 80&#xa0;mg QD regimen (determination coefficient: 52.2%).</p> Conclusion <p>Overall, our findings showed that an adjustment of the initial asciminib dose may be needed based on genotyping information for the <i>NR1I2</i> -25385C &gt; T polymorphism and the body weight of the patient; however, further prospective studies are necessary.</p>

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Influence of pharmacokinetics-related polymorphisms on asciminib exposure in patients with Japanese chronic myeloid leukemia

  • 期刊论文

  • 发表日期：

    2026年1月19日

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  • Naoto Takahashi,
  • Yumiko Akamine,
  • Masatomo Miura

摘要

Purpose

The effects of polymorphisms in CYP3A4, UGT2B7, ABCB1, ABCG2, ABCC2, NR1I2, and AHR genes on asciminib exposure were evaluated in Japanese patients with chronic myeloid leukemia.

Methods

Plasma concentrations of asciminib (40 mg twice daily [BID] or 80 mg once daily [QD]) were measured by high-performance liquid chromatography. Statistical analysis was performed using SPSS (P < 0.05).

Results

For both regimens, the median asciminib area under the concentration–time curve (AUC) was significantly higher in female than in male patients (P = 0.009 and 0.004, respectively). Significant correlations were observed between the asciminib AUC of 40 mg BID or 80 mg QD and body weight (P = 0.042 and < 0.001, respectively). The asciminib AUC0-12 of 40 mg BID in patients with the -25385 T allele of the NR1I2 -25385C > T polymorphism was significantly lower than that in patients with the -25385C/C genotype (5363 and 10607 ng∙h/mL, respectively, P = 0.001). In multiple regression analyses, the NR1I2 -25385C > T polymorphism (P = 0.001) and female sex (P = 0.002) were independently predictive of a higher asciminib AUC0-12 for the 40 mg BID regimen (determination coefficient: 52.8%), whereas body weight (P < 0.001) and female sex (P = 0.047) were independently predictive of a higher asciminib AUC0-24 for the 80 mg QD regimen (determination coefficient: 52.2%).

Conclusion

Overall, our findings showed that an adjustment of the initial asciminib dose may be needed based on genotyping information for the NR1I2 -25385C > T polymorphism and the body weight of the patient; however, further prospective studies are necessary.