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Background <p>The combination of venetoclax (VEN) with hypomethylating agents (HMAs) has emerged as a new standard treatment for older or unfit patients with acute myeloid leukemia (AML). However, the predictive factors for VEN/HMA efficacy remain unclear. In our study, we performed the first analysis of the impact of KIT mutations on therapeutic outcomes in newly diagnosed AML patients undergoing VEN/HMA regimens.</p> Methods <p>In this retrospective study, we included 16 KIT-mutant AML patients receiving VEN/HMA (Cohort A), 141 KIT-wild-type AML patients receiving VEN/HMA (Cohort B), and 69 KIT-mutant AML patients receiving intensive chemotherapy (IC) (Cohort C). We compared the differences in therapeutic efficacy among the different cohorts. Furthermore, we conducted multivariate analyses in patients receiving VEN/HMA to identify factors influencing therapeutic outcomes.</p> Results <p>Compared to Cohort B, Cohort A exhibited significantly lower overall response rate (ORR) (18.8% vs. 72.3%, <i>p</i> &lt; 0.001) and measurable residual disease (MRD) negativity rate (18.8% vs. 68.1%, <i>p</i> &lt; 0.001), with a shorter median event-free survival (EFS) (1.9&#xa0;months vs. 7.8&#xa0;months, <i>p</i> &lt; 0.001). No significant difference in overall survival (OS) was observed. Among KIT-mutant patients, IC showed superior ORR (78.3% vs. 18.8%, <i>p</i> &lt; 0.001), MRD negativity rate (75.4% vs. 18.8%, <i>p</i> &lt; 0.001), and EFS (12.2&#xa0;months vs. 1.9&#xa0;months, <i>p</i> &lt; 0.001) compared to VEN/HMA. No significant difference in OS was observed between the two cohorts. Multivariate analysis confirmed KIT mutations as an independent predictor of lower ORR (OR 0.020, 95% CI 0.002–0.211, <i>p</i> = 0.001) and shorter EFS (HR 6.318, 95% CI 2.659–15.012, <i>p</i> &lt; 0.001).</p> Conclusions <p>Our findings suggest that KIT mutations are associated with poor response and shorter EFS in AML patients treated with VEN/HMA, highlighting the importance of KIT mutation status in risk stratification and treatment selection.</p>

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Impact of KIT mutation on efficacy of venetoclax and hypomethylating agents in newly diagnosed acute myeloid leukemia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月2日

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  • Wenxiu Shu,
  • Qianqian Yang,
  • Donghua He,
  • Yi Li,
  • Jing Le,
  • Qianqian Cai,
  • Hui Dai,
  • Liufei Luo,
  • Bingrong Chen,
  • Yuan Gong,
  • Dian Jin

摘要

Background

The combination of venetoclax (VEN) with hypomethylating agents (HMAs) has emerged as a new standard treatment for older or unfit patients with acute myeloid leukemia (AML). However, the predictive factors for VEN/HMA efficacy remain unclear. In our study, we performed the first analysis of the impact of KIT mutations on therapeutic outcomes in newly diagnosed AML patients undergoing VEN/HMA regimens.

Methods

In this retrospective study, we included 16 KIT-mutant AML patients receiving VEN/HMA (Cohort A), 141 KIT-wild-type AML patients receiving VEN/HMA (Cohort B), and 69 KIT-mutant AML patients receiving intensive chemotherapy (IC) (Cohort C). We compared the differences in therapeutic efficacy among the different cohorts. Furthermore, we conducted multivariate analyses in patients receiving VEN/HMA to identify factors influencing therapeutic outcomes.

Results

Compared to Cohort B, Cohort A exhibited significantly lower overall response rate (ORR) (18.8% vs. 72.3%, p < 0.001) and measurable residual disease (MRD) negativity rate (18.8% vs. 68.1%, p < 0.001), with a shorter median event-free survival (EFS) (1.9 months vs. 7.8 months, p < 0.001). No significant difference in overall survival (OS) was observed. Among KIT-mutant patients, IC showed superior ORR (78.3% vs. 18.8%, p < 0.001), MRD negativity rate (75.4% vs. 18.8%, p < 0.001), and EFS (12.2 months vs. 1.9 months, p < 0.001) compared to VEN/HMA. No significant difference in OS was observed between the two cohorts. Multivariate analysis confirmed KIT mutations as an independent predictor of lower ORR (OR 0.020, 95% CI 0.002–0.211, p = 0.001) and shorter EFS (HR 6.318, 95% CI 2.659–15.012, p < 0.001).

Conclusions

Our findings suggest that KIT mutations are associated with poor response and shorter EFS in AML patients treated with VEN/HMA, highlighting the importance of KIT mutation status in risk stratification and treatment selection.