Blinatumomab for Replacing Chemotherapy in Pediatric Acute Lymphoblastic Leukemia.

Methods

We randomly assigned, in a 1:1 ratio, children with high-risk B-cell ALL to receive two cycles of blinatumomab (blinatumomab group) or two cycles of chemotherapy (control group) after consolidation.

我们在1:1的比例中随机分配了高危B细胞ALL儿童患者，以接受两个周期的Blinatumomab治疗（Blinatumomab组）或两个周期的传统化疗（对照组），在巩固治疗后进行。

The primary end point was event-free survival as evaluated in a time-to-event analysis; the duration of event-free survival was defined as the time from randomization to the first event among resistance to protocol treatment, relapse, second cancer, or death from any cause.

主要终点是通过时间至事件分析评估的无事件生存期；无事件生存期的持续时间被定义为从随机分组到首次出现对方案治疗抵抗、复发、第二种癌症或任何原因导致的死亡的时间。

Our primary objective was to evaluate whether the 4-year event-free survival would be 10 percentage points higher in the blinatumomab group than in the control group.

我们的主要目标是评估Blinatumomab组的4年无事件生存率是否会比对照组高出10个百分点。

Results

Overall, 709 of 768 eligible patients (92.3%) underwent randomization; 358 were assigned to the blinatumomab group and 351 to the control group.

总体而言，768名符合条件的患者中有709名（92.3%）进行了随机分组；358名被分配到Blinatumomab组，351名被分配到对照组。

A planned interim analysis at a median follow-up of 2.9 years showed an estimated 4-year event-free survival of 83.0% (95% confidence interval[CI], 77.4 to 87.4) in the blinatumomab group and 70.3% (95% CI, 63.8 to 75.9) in the control group (P = 0.0002 in an intention-to-treatanalysis).

在中位随访2.9年时进行的计划中期分析显示，Blinatumomab组的估计4年无事件生存率为83.0%（95%置信区间[CI]，77.4至87.4），对照组为70.3%（95%置信区间，63.8至75.9）（意向治疗分析的P = 0.0002）。

The estimated hazard ratiofor a primary end-point event (blinatumomab vs. control) was 0.51 (95% CI, 0.35 to 0.73) as assessed with a Cox model.

使用Cox模型评估的主要终点事件（Blinatumomab与对照组）的估计风险比为0.51（95%置信区间，0.35至0.73）。

Infection related to the trial treatment occurred in 23.9% of patients in the blinatumomab group and in 69.4% of those in the control group (P<0.001).

与试验治疗相关的感染发生在Blinatumomab组的23.9%的患者中，以及对照组的69.4%的患者中（P<0.001）。

Life-threatening adverse events occurred in 2 patients (0.5%) in the blinatumomab group, including one (in 0.3%) that was fatal, and in 16 patients (4.7%) in the control group.

在使用毕利妥单抗的组别中，有2名患者（0.5%）发生了危及生命的不良事件，包括1名（0.3%）致命事件，在对照组中有16名患者（4.7%）发生了此类事件。

Neurotoxic events were reported in 12.0% and 3.2%, respectively (P<0.001).

神经毒性事件分别在12.0%和3.2%的患者中报告（P<0.001）。

Cytokine release syndrome of grade 2 or higher occurred in 1.1% of patients in the blinatumomab group.

在毕利妥单抗组中，有1.1%的患者发生了2级或更高级别的细胞因子释放综合征。

Conclusions

In children with newly diagnosed high-risk B-cell ALL, replacement of two cycles of highly toxic conventional chemotherapy with blinatumomab resulted in a significantly greater percentage of patients with event-free survival at 4 years.

对于新诊断的高危B细胞ALL儿童，用毕利妥单抗替换两周期高毒性的传统化疗，使得4年后无事件生存的患者百分比显著增加。

(Funded by Deutsche Krebshilfe and others; AIEOP-BFM ALL 2017 EudraCT number, 2016-001935-12; EU Clinical Trials number, 2023-509856-32-00; and ClinicalTrials.gov number, NCT03643276.).

该项目由德国癌症援助协会和其他机构资助；AIEOP-BFM ALL 2017 EudraCT编号，2016-001935-12；EU临床试验编号，2023-509856-32-00；以及ClinicalTrials.gov编号，NCT03643276。