AAML1831: A Phase III Trial Comparing Standard Induction Therapy With CPX-351 in De Novo Pediatric AML: A Report From the Children's Oncology Group.

We hypothesized that CPX-351 given during induction 1 and 2 would improve outcomes compared with DA.

我们假设在诱导治疗的第1和第2周期给予CPX-351会比DA治疗改善结果。

patients_and_methods

Patients (21 years and younger) were randomly assigned to two cycles of DA induction (arm A = DA) or CPX-351 (arm B = CPX-351).

患者（21岁及以下）被随机分配到两个周期的DA诱导治疗（A组=DA）或CPX-351（B组=CPX-351）。

All patients also received gemtuzumab ozogamicin in induction 1.

所有患者在诱导治疗第1周期也接受了gemtuzumab ozogamicin治疗。

Postinduction chemotherapy was according to risk assignment made at the end of induction 1 (EOI1).

诱导治疗后的化疗根据诱导治疗第1周期结束时的风险评估进行。

Those with high-risk (HR) AML received consolidation with allogeneic hematopoietic stem-cell transplantation (HSCT), whereas low-risk (LR) patients received chemotherapy alone.

高危（HR）AML患者接受异基因造血干细胞移植(HSCT)巩固治疗，而低危（LR）患者仅接受化疗。

Protocol-specified interim analysis monitored efficacy and futility of CPX-351 induction with respect to the primary end point, event-free survival (EFS) from study entry.

协议规定的中期分析监测了CPX-351诱导治疗相对于主要终点——从研究开始的无事件生存（EFS）——的有效性和无效性。

Disease-free survival (DFS) was calculated to determine the impact of EOI1 risk assignment.

无病生存（DFS）的计算用来确定EOI1风险评估的影响。

Results

Seven hundred twenty-one eligible patients with FLT3 wild-type AML were randomly assigned to DA (n = 358) or CPX-351 (n = 363).

共有721名符合条件的FLT3野生型急性髓细胞性白血病（AML）患者被随机分配到DA组（n = 358）或CPX-351组（n = 363）。

Interim analysis determined that the futility monitoring rule was crossed because of inferior EFS in the CPX-351 arm and the random assignment was stopped.

中期分析确定，由于CPX-351组的无事件生存（EFS）较差，触发了无效监测规则，因此停止了随机分配。

The two-year EFS from study entry was 62.2% for DA versus 51.2% for CPX-351 (P = .011).

从研究开始的两年无事件生存（EFS）为DA组的62.2%，而CPX-351组为51.2%（P = .011）。

DFS for patients with HR AML was comparable for both arms.

高危（HR）急性髓细胞性白血病（AML）患者的无病生存（DFS）在两组中相当。

However, DFS was significantly lower and cumulative incidenceof relapse (CIR) was higher for LR patients assigned to CPX-351 versus DA (2-year DFS from EOI1: DA: 73.8% v CPX-351 57.5% [P = .001]; 2-year CIR Arm DA: 23.6% v CPX-351: 39.9% [P = .001]).

然而，对于低危（LR）患者，被分配到CPX-351组的无病生存（DFS）显著较低，累积复发率（CIR）较高（从EOI1开始的2年DFS：DA组为73.8%，CPX-351组为57.5% [P = .001]；2年CIR：DA组为23.6%，CPX-351组为39.9% [P = .001]）。

Conclusions

CPX-351 was inferior to DA induction in the AAML1831 trial with differential EFS largely driven by events in LR patients.

在AAML1831试验中，CPX-351在诱导治疗中劣于DA，差异化的无事件生存（EFS）主要由低危（LR）患者的事件驱动。