CPX-351 selectively benefits patients with AML and myelodysplasia-related mutations in the pivotal randomized trial.

We evaluated whether the overall survival(OS) benefit of CPX-351 over standard cytarabine plus anthracycline (7+3) therapy is confined to molecularly defined AML subgroups by performing DNA sequencing in 184 patients enrolled in the pivotal phase 3 randomized trial. Patients were categorized hierarchically based on gene mutations: (1) TP53-AML, (2) DDX41-AML, (3) myelodysplasia-related AML (AML-MR) defined by the World Health Organization fifth edition criteria, or (4) other-AML.

我们评估了CPX-351与标准的阿糖胞苷加蒽环类（7+3）疗法相比，在总生存（OS）上的优势是否仅限于分子定义的AML亚组，通过对184名参与关键性III期随机试验的患者进行DNA测序。患者基于基因突变进行分层分类：（1）TP53-AML，（2）DDX41-AML，（3）根据世界卫生组织第五版标准定义的骨髓增生异常相关AML（AML-MR），或（4）其他AML。

TP53-AML was subclassified as single (TP53single) or multihit (TP53multi) based on the number of alleles altered via mutation, deletion, or copy neutral loss of heterozygosity.

TP53-AML根据等位基因通过突变、缺失或拷贝中性杂合性丧失改变的数量被细分为单突变型（TP53single）或多突变型（TP53multi）。

Two-year OS differed significantly across molecular subgroups: TP53-AML (7%), AML-MR (19%), other-AML (37%), and DDX41-AML (70%) (P< .001).

两年总生存率在分子亚组间存在显著差异：TP53-AML（7%）、AML-MR（19%）、其他AML（37%）和DDX41-AML（70%）（P< .001）。

CPX-351 improved survival in patients with AML-MR compared with 7+3 (median, 9.7 vs 6.8 months; P = .037), with no benefit in TP53-AML or other-AML.

CPX-351与7+3方案相比，改善了急性髓细胞性白血病伴多药耐药（AML-MR）患者的生存期（中位生存期，9.7个月对比6.8个月；P = .037），但在TP53突变的AML或其他类型的AML患者中未见生存获益。

For patients undergoing transplantation, CPX-351 improved 2-year survival (76% vs 27%; P< .01), an effect primarily observed in AML-MR.

对于接受移植的患者，CPX-351改善了2年生存率（76%对比27%；P< .01），这种效果主要在急性髓细胞性白血病伴多药耐药（AML-MR）患者中观察到。

Multivariable analysis confirmed the independent association with survival of both CPX-351 and hematopoietic cell transplantation in AML-MR.

多变量分析证实了CPX-351和造血细胞移植在急性髓细胞性白血病-多药耐药中的独立生存关联。

TP53multi demonstrated significantly worse survival than TP53single (median, 3.8 vs 7.0 months; P = .004).

TP53multi显示出比TP53single显著更差的生存率（中位数，3.8 vs 7.0个月；P = .004）。

The OS benefit of CPX-351 observed in the trial was driven by AML-MR with no benefit of CPX-351 in TP53-AML, in which the primary prognostic factor was allelic state.

该试验观察到CPX-351带来的总生存（OS）益处主要由急性髓细胞性白血病-多药耐药（AML-MR）驱动，而在TP53突变的AML中，CPX-351没有显示出任何益处，其中主要的预后因素是等位基因状态。

This trial was registered at www.clinicaltrials.gov as #NCT01696084.

该试验已在www.clinicaltrials.gov上注册，注册号为#NCT01696084。