Homoharringtonine Added to Venetoclax and Azacitidine Improves Outcome and Mitigates Genetic Impact in Relapsed/Refractory AML: A Multi-center Cohort Study

IF 10 1区医学 Q1 ONCOLOGY

Clinical Cancer Research Pub Date : 2024-11-12 DOI:10.1158/1078-0432.ccr-24-1332

Guopan Yu, Yu Zhang, Sijian Yu, Zhao Yin, Guangyang Weng, Na Xu, Xin Du, Dongjun Lin, Jie Xiao, Zhiqiang Sun, Hongyu Zhang, Xinquan Liang, Ziwen Guo, Weihua Zhao, Min Dai, Zhiping Fan, Li Xuan, Hui Liu, Dan Xu, Jieyu Ye, Xuejie Jiang, Pengcheng Shi, Hua Jin, Qifa Liu

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引用次数: 0

Abstract

Purpose: We investigated whether homoharringtonine (HHT) added to venetoclax (VEN) plus azacitidine (VA) could improve outcomes and counteract the negative effects of genetic patterns in patients with relapsed/refractory acute myeloid leukemia (RR-AML). Experimental Design: A multi-center, retrospective, cohort study of the response and genetic patterns of response to the VA plus HHT (VAH) versus the VA regimens as salvage treatment in patients with RR-AML was performed. The endpoints were the rates of composite complete remission (CRc), measurable residual disease (MRD), event-free survival (EFS), overall survival (OS), and relapse between VAH and VA groups. Results: A total of 321 patients (VAH, n=172; VA, n=149) were analyzed. Compared to VA, VAH significantly improved the rates of CRc (44.3% vs. 66.3%, P<0.001), MRD-negativity (34.8% vs. 59.3%, P=0.002), prolonged OS (median: 15.1 months vs. not reached, P <0.001), and EFS (median: 3.8 vs. 13.0 months, P<0.001). VAH significantly mitigated the negative impact on VA efficacy of mutated FLT3-ITD/TKD, N/KRAS, and t(8;21)/AML1-ETO, as well as the relatively unfavorable effects of the TET2 and DNMT3A mutations. VAH significantly enhanced the response of patients with non-adverse European LeukemiaNet (ELN) risk, with a trend towards improved response in those with adverse ELN risk, complex karyotype, and DNMT3A+FLT3+NPM1+. The incidence of grade 3 or higher adverse events was comparable between the two groups. Conclusions: Our findings suggest the addition of HHT to VA might enhance response and mitigate the negative impact of certain genetic patterns in RR-AML while being well tolerated.

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在 Venetoclax 和阿扎胞苷基础上加用 Homoharringtonine 可改善复发/难治性急性髓细胞白血病患者的预后并减轻遗传影响：一项多中心队列研究

目的：我们研究了在 Venetoclax（VEN）加阿扎胞苷（VA）的基础上添加同型异构化酶（HHT）能否改善复发/难治性急性髓性白血病（RR-AML）患者的预后并抵消遗传模式的负面影响。实验设计：进行了一项多中心、回顾性、队列研究，探讨了VA加HHT（VAH）与VA方案作为RR-AML患者挽救治疗的反应和遗传模式。研究终点是VAH组和VA组之间的复合完全缓解率（CRc）、可测量残留疾病率（MRD）、无事件生存率（EFS）、总生存率（OS）和复发率。结果共分析了321名患者（VAH，n=172；VA，n=149）。与VA相比，VAH显著提高了CRc率（44.3% vs. 66.3%，P<0.001）、MRD阴性率（34.8% vs. 59.3%，P=0.002）、OS延长率（中位数：15.1个月 vs. 未达到，P<0.001）和EFS（中位数：3.8个月 vs. 13.0个月，P<0.001）。VAH明显减轻了FLT3-ITD/TKD、N/KRAS和t（8；21）/AML1-ETO突变对VA疗效的负面影响，以及TET2和DNMT3A突变的相对不利影响。VAH能明显增强非欧洲白血病网络（ELN）不良风险患者的反应，ELN不良风险、复杂核型和DNMT3A+FLT3+NPM1+患者的反应有改善趋势。两组患者的3级或以上不良反应发生率相当。结论我们的研究结果表明，在VA中加入HHT可能会增强RR-AML的反应并减轻某些遗传模式的负面影响，同时具有良好的耐受性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Cancer Research 医学-肿瘤学

CiteScore

20.10

自引率

1.70%

发文量

1207

审稿时长

2.1 months

期刊介绍： Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.