Agarwal Sonal, Kowalski Andrew, Schiffer Molly, Zhao Jennifer, Bewersdorf Jan Philipp, Zeidan Amer M
Department of Pharmacy, Yale New Haven Hospital, New Haven, CT, USA.
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
Expert Rev Hematol. 2021 Feb;14(2):199-210. doi: 10.1080/17474086.2021.1876559. Epub 2021 Feb 8.
Acute myeloid leukemia (AML) is an aggressive malignancy with poor prognosis and high rates of relapse, especially in elderly patients who are ineligible to receive intensive chemotherapy. Venetoclax, an oral BCL-2 inhibitor, is approved by the Food and Drug Administration in combination with hypomethylating agents or low-dose cytarabine in newly-diagnosed AML patients who are ineligible to receive intensive chemotherapy. Confirmatory phase III VIALE-A and VIALE-C trials showed a composite complete remission rate of 66.4% and 48%, respectively. Thus, further validating venetoclax as an attractive therapeutic option in the AML treatment landscape.
A review of venetoclax in AML, focusing on preclinical and clinical data, toxicity profile, and mechanisms of resistance; and its strengths and weaknesses in regards to its current and future role in AML treatment is discussed. To find relevant studies, authors searched PubMed/Medline and ClinicalTrials.gov.
The introduction of venetoclax-based combination therapies has greatly expanded the therapeutic options for elderly and chemotherapy-ineligible AML patients. Additional studies with extended follow-up are necessary to address remaining open questions such as (I) durability of responses, (II) head-to-head comparisons with intensive chemotherapy in selected patients (e.g. mutations), and (III) novel triplet combinations using an HMA-venetoclax backbone.
急性髓系白血病（AML）是一种侵袭性恶性肿瘤，预后较差且复发率高，尤其是在不符合接受强化化疗条件的老年患者中。维奈克拉是一种口服BCL-2抑制剂，已获美国食品药品监督管理局批准，可与去甲基化药物或小剂量阿糖胞苷联合用于新诊断的不符合接受强化化疗条件的AML患者。验证性III期VIALE-A和VIALE-C试验显示，复合完全缓解率分别为66.4%和48%。因此，进一步验证了维奈克拉在AML治疗领域是一种有吸引力的治疗选择。
对维奈克拉在AML中的应用进行综述，重点关注临床前和临床数据、毒性特征及耐药机制；并讨论其在AML治疗当前及未来作用方面的优缺点。为查找相关研究，作者检索了PubMed/Medline和ClinicalTrials.gov。
基于维奈克拉的联合疗法的引入极大地扩展了老年及不符合化疗条件的AML患者的治疗选择。有必要开展更多延长随访的研究，以解决剩余的未决问题，如（I）缓解的持久性，（II）在特定患者（如突变患者）中与强化化疗的直接比较，以及（III）使用去甲基化药物-维奈克拉为主的新型三联组合。
