Department of Medicine, Division of Hematology-Oncology and the Abramson Cancer Center at the University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania USA.
Curr Opin Hematol. 2018 Mar;25(2):81-89. doi: 10.1097/MOH.0000000000000411.
Precious few drugs were successfully developed for acute myeloid leukemia (AML) over the past decades, despite a dramatic expansion of our understanding of its molecular underpinnings during this time. Then in 2017, a wave of new drugs suddenly became approved. This review serves to introduce the newly available drugs, discuss their impact upon therapy, and highlight additional novel agents that are waiting in the wings.
Newly approved agents in AML include a tyrosine kinase inhibitor for patients with FMS-like tyrosine kinase 3 (FLT3) mutations, an inhibitor of mutant isocitrate dehydrogenase (IDH2), and two novel agents using antibody-delivered or liposome-delivered cytotoxics. All of these new agents have demonstrable activity in AML and several have improved survival in randomized studies. In addition to these agents, promising data from other inhibitors of FLT3, IDH1, and B-cell lymphoma 2 (BCL2) will be discussed.
Response, survival, and symptom burden of AML therapy are all improving through novel agents. As many of the newly approved drugs benefit-specific genetic subsets, a new priority has emerged to increase the speed of diagnostic genomic studies as a means to guide frontline therapy. This will ensure patients are optimally categorized and treated with to the most rational agents.
目的综述：尽管在过去几十年中，我们对急性髓系白血病（AML）的分子基础有了更深入的了解，但成功开发的药物却寥寥无几。直到 2017 年，一波新的药物突然获得批准。本文旨在介绍新的药物，讨论它们对治疗的影响，并强调其他等待批准的新型药物。
最新发现：AML 新批准的药物包括针对 FMS 样酪氨酸激酶 3（FLT3）突变患者的酪氨酸激酶抑制剂、突变型异柠檬酸脱氢酶（IDH2）抑制剂，以及两种使用抗体或脂质体递送细胞毒素的新型药物。所有这些新药物在 AML 中都具有明显的活性，并且在随机研究中都改善了生存。除了这些药物外，还将讨论其他 FLT3、IDH1 和 B 细胞淋巴瘤 2（BCL2）抑制剂的有前途的数据。
总结：通过新型药物，AML 治疗的反应、生存和症状负担都得到了改善。由于许多新批准的药物都针对特定的遗传亚型，因此一个新的重点是加快诊断性基因组研究的速度，作为指导一线治疗的手段。这将确保患者得到最佳分类，并使用最合理的药物进行治疗。
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