Optimization of idarubicin and cytarabine induction regimen with homoharringtonine for newly diagnosed acute myeloid leukemia patients based on the peripheral blast clearance rate: A single‐arm, phase 2 trial (RJ‐AML 2014)
Optimization of idarubicin and cytarabine induction regimen with homoharringtonine for newly diagnosed acute myeloid leukemia patients based on the peripheral blast clearance rate: A single‐arm, phase 2 trial (RJ‐AML 2014)
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DOI：
10.1002/ajh.26386
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发表时间：
2021-10
影响因子：
12.8
通讯作者：
Yunxiang Zhang;Xiaoyang Li;Xiang-Qin Weng;Yang Shen;Yú Chen;Yu Zheng;Hui-jin Zhao;J. You
中科院分区：
文献类型：
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作者：
Yunxiang Zhang;Xiaoyang Li;Xiang-Qin Weng;Yang Shen;Yú Chen;Yu Zheng;Hui-jin Zhao;J. You
个体化化疗是急性髓系白血病 (AML) 治疗的前沿技术，在过去十年中已适度改善预后。通过流式细胞术监测诱导过程中的外周血原始细胞负荷在评估治疗反应方面显示出重要价值。我们之前的研究报告将第 5 天外周原始细胞清除率 (D5-PBCR) 作为早期治疗反应的指标，而 D5-PBCR (+) 患者的预后较差。我们对 D5-PBCR (+) 患者进行了目前的 2 期试验，在传统的蒽环类和阿糖胞苷诱导方案中引入高三尖杉酯碱 (HHT) 进行早期干预。主要终点是完全缓解（CR）。该研究招募了 151 名患者，其中 65 名患者为 D5-PBCR (+)，55 名患者通过添加 HHT 完成诱导。诱导一个疗程后的总体 CR 率为 84.4%，其中 D5-PBCR (-) 组和 D5-PBCR (+) 组分别为 87.5% 和 80.0%。两组之间 3/4 级不良事件的发生率相当。中位随访时间为 53.1 个月，整个队列的中位总生存期 (OS) 尚未达到，中位无事件生存期 (EFS) 为 42.2 个月。 D5-PBCR (-) 和 D5-PBCR (+) 组之间的 OS 和 EFS 均未显示出显着差异。与历史数据相比，D5-PBCR (+) 组的 OS (p = .020) 和 EFS (p = .020) 均显着改善。总之，根据D5-PBCR优化伊达比星和阿糖胞苷诱导化疗对于初诊AML患者是可行的。 HHT 的添加表现出良好的功效和安全性。
Individualized chemotherapy, which is at the forefront of acute myeloid leukemia (AML) treatment, has moderately improved outcomes over the past decade. Monitoring the peripheral blood blast burden during induction by flow cytometry has shown significant value in the evaluation of treatment responses. Our previous study reported the day 5 peripheral blast clearance rate (D5‐PBCR) as an indicator of early treatment response, and D5‐PBCR (+) patients showed poor outcomes. We performed the present phase 2 trial of early intervention in D5‐PBCR (+) patients with homoharringtonine (HHT) introduced in the traditional induction regimen with anthracycline and cytarabine. The primary endpoint was complete remission (CR). This study enrolled 151 patients, 65 patients were D5‐PBCR (+) and 55 patients completed induction with HHT addition. The overall CR rate after one course of induction was 84.4%, with 87.5% and 80.0% for the D5‐PBCR (−) and D5‐PBCR (+) groups, respectively. The incidence of grade 3/4 adverse events was comparable between the two groups. At the median follow‐up of 53.1 months, median overall survival (OS) was not reached in the entire cohort, and median event‐free survival (EFS) was 42.2 months. Neither the OS nor EFS showed significant differences between the D5‐PBCR (−) and D5‐PBCR (+) groups. Compared to historical data, significant improvements in both OS (p = .020) and EFS (p = .020) were observed in the D5‐PBCR (+) group. In conclusion, optimization of induction chemotherapy with idarubicin and cytarabine according to D5‐PBCR is feasible in patients with newly diagnosed AML. The addition of HHT demonstrated a good efficacy and safety profile.