Reformulating acute myeloid leukemia: liposomal cytarabine and daunorubicin (CPX-351) as an emerging therapy for secondary AML.
Reformulating acute myeloid leukemia: liposomal cytarabine and daunorubicin (CPX-351) as an emerging therapy for secondary AML.
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DOI：
10.2147/ott.s141212
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发表时间：
2018
影响因子：
4
通讯作者：
Brunner AM
中科院分区：
文献类型：
--
作者：
Chen EC;Fathi AT;Brunner AM
尽管人们对急性髓性白血病（AML）的病理生物学的了解越来越多，但结果仍然令人沮丧，特别是对于60岁以上的患者，治疗相关AML （tAML）和继发性AML （sAML）的人群丰富。几十年来，AML的标准治疗一直是阿糖胞苷和柔红霉素联合使用，通常以“7 + 3”诱导方式联合使用。2017年，美国食品和药物管理局（FDA）批准了一种脂质体包裹的柔红霉素和阿糖胞苷（CPX-351, Vyxeos）用于治疗新诊断的AML或AML伴骨髓增生异常相关改变（AML- mrcs）。CPX-351被设计为分别以固定的5:1摩尔比递送阿糖胞苷和柔红霉素，基于比例给药可能比在其最大耐受剂量下递送任何一种药物更有效的假设。在一项针对60-75岁老年sAML患者的III期试验中，CPX-351被比较为“7 + 3”，并且与更高的总生存期、无事件生存期、更高的完全缓解（CR）率和CR合并不完全血液学恢复（CRi）相关。这些数据是批准这种新药用于治疗AML的基础，但关于如何在AML亚群中最好地施用这种药物的问题仍然存在。未来的方向包括评估CPX-351的剂量强化，将该药物与靶向治疗相结合，以及更好地了解tAML和AML-MRC的改善反应机制，这两种实体历来对细胞毒性药物反应较低。总之，CPX-351为AML治疗领域带来了令人兴奋的新变化。
Despite increasing understanding of the pathobiology of acute myeloid leukemia (AML), outcomes remain dismal particularly for patients over the age of 60 years, a population enriched for therapy-related AML (tAML) and secondary AML (sAML). For decades, the standard of care for AML has been the combination of cytarabine and daunorubicin, typically delivered in combination as “7 + 3” induction. In 2017, a liposomal-encapsulated combination of daunorubicin and cytarabine (CPX-351, Vyxeos) was approved by the US Food and Drug Administration (FDA) for use in the treatment of newly diagnosed tAML or AML with myelodysplasia-related changes (AML-MRCs). CPX-351 was designed to deliver a fixed 5:1 molar ratio of cytarabine and daunorubicin, respectively, based on the hypothesis that ratiometric dosing may be more effective than the delivery of either drug at their maximum tolerated dose. In a Phase III trial of older patients with sAML aged 60–75 years, CPX-351 was compared to “7 + 3” and was associated with a higher overall survival, event-free survival, and higher rates of complete remission (CR) and CR with incomplete hematologic recovery (CRi). These data were the basis for the approval of this new drug for use in the treatment of AML, but questions remain regarding how to best administer this agent across AML subgroups. Future directions include evaluating dose intensification with CPX-351, combining this agent with targeted therapies, and better understanding the mechanism of improved responses in tAML and AML-MRC, two entities that are historically less responsive to cytotoxic agents. In summary, CPX-351 offers an exciting new change to the landscape of AML therapy.