文章：

基于维奈托克的化疗在急性和慢性髓系肿瘤中的应用：文献综述与实践要点

Venetoclax-based chemotherapy in acute and chronic myeloid neoplasms: literature survey and practice points

原文发布日期：2020-11-23

DOI: 10.1038/s41408-020-00388-x

类型: Review Article

开放获取: 是

英文摘要：

Venetoclax (VEN), a small-molecule inhibitor of B cell leukemia/lymphoma-2, is now FDA approved (November 2018) for use in acute myeloid leukemia (AML), specific to newly diagnosed elderly or unfit patients, in combination with a hypomethylating agent (HMA; including azacitidine or decitabine) or low-dose cytarabine. A recent phase-3 study compared VEN combined with either azacitidine or placebo, in the aforementioned study population; the complete remission (CR) and CR with incomplete count recovery (CRi) rates were 28.3% and 66.4%, respectively, and an improvement in overall survival was also demonstrated. VEN-based chemotherapy has also shown activity in relapsed/refractory AML (CR/CRi rates of 33–46%), high-risk myelodysplastic syndromes (CR 39% in treatment naïve, 5–14% in HMA failure), and blast-phase myeloproliferative neoplasm (CR 25%); in all instances, an additional fraction of patients met less stringent criteria for overall response. Regardless, venetoclax-induced remissions were often short-lived (less than a year) but long enough to allow some patients transition to allogeneic stem cell transplant. Herein, we review the current literature on the use of VEN-based combination therapy in both acute and chronic myeloid malignancies and also provide an outline of procedures we follow at our institution for drug administration, monitoring of adverse events and dose adjustments.
 

摘要翻译： 

维奈托克(VEN)是一种B细胞白血病/淋巴瘤-2小分子抑制剂，已于2018年11月获得美国FDA批准，用于联合去甲基化药物（包括阿扎胞苷或地西他滨）或低剂量阿糖胞苷治疗新确诊的老年或不耐受强化疗的急性髓系白血病(AML)患者。最近一项三期研究在上述研究人群中比较了VEN联合阿扎胞苷与安慰剂的疗效：完全缓解(CR)率和血细胞计数不完全恢复的完全缓解(CRi)率分别为28.3%和66.4%，总生存期也显示出改善。基于VEN的化疗方案在复发/难治性AML（CR/CRi率为33-46%）、高危骨髓增生异常综合征（初治患者CR率为39%，HMA治疗失败患者为5-14%）和急变期骨髓增殖性肿瘤（CR率为25%）中也显示出活性；在所有情况下，另有部分患者达到相对宽松的总体缓解标准。尽管维奈托克诱导的缓解通常持续时间较短（不足一年），但足以使部分患者过渡至异基因干细胞移植。本文综述了当前关于基于VEN的联合疗法在急慢性髓系恶性肿瘤中应用的文献，并概述了我院在药物给药、不良事件监测和剂量调整方面遵循的规程。

原文链接：

Venetoclax-based chemotherapy in acute and chronic myeloid neoplasms: literature survey and practice points