BACKGROUND B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common childhood cancer. Despite a high overall cure rate, relapsed B-cell ALL remains a leading cause of cancer-related death among children. The addition of the bispecific T-cell engager molecule blinatumomab (an anti-CD19 and anti-CD3 single-chain molecule) to therapy for newly diagnosed standard-risk (as defined by the National Cancer Institute) B-cell ALL in children may improve outcomes. METHODS We conducted a phase 3 trial involving children with newly diagnosed standard-risk B-cell ALL who had an average or high risk of relapse. Patients were randomly assigned to receive chemotherapy alone or chemotherapy plus two nonsequential 28-day cycles of blinatumomab. The primary end point was disease-free survival. RESULTS The data and safety monitoring committee reviewed the results from the first interim efficacy analysis, which included 1440 patients who had undergone randomization (722 to chemotherapy alone and 718 to blinatumomab and chemotherapy) and recommended early termination of randomization. At a median follow-up of 2.5 years, the estimated 3-year disease-free survival (±SE) was 96.0±1.2% with blinatumomab and chemotherapy and 87.9±2.1% with chemotherapy alone (difference in restricted mean survival time, 72 days; 95% confidence interval, 36 to 108; P<0.001 by stratified log-rank test). The estimated 3-year disease-free survival among patients with an average relapse risk was 97.5±1.3% with blinatumomab and chemotherapy and 90.2±2.3% with chemotherapy alone; among those with a high relapse risk, the corresponding values were 94.1±2.5% and 84.8±3.8%. Cytokine release syndrome, seizures, and sepsis of grade 3 or higher were rare during blinatumomab cycles, but the overall incidence of nonfatal sepsis and catheter-related infections was significantly higher among patients with an average relapse risk who had been assigned to receive blinatumomab and chemotherapy than among those assigned to receive chemotherapy alone. CONCLUSIONS Adding blinatumomab to combination chemotherapy in patients with newly diagnosed childhood standard-risk B-cell ALL of average or high risk of relapse significantly improved disease-free survival. (Funded by the National Institutes of Health and others; AALL1731 ClinicalTrials.gov number, NCT03914625.).

中文翻译：

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Blinatumomab 治疗儿童标准风险 B 细胞急性淋巴细胞白血病。


背景 B 细胞急性淋巴细胞白血病 （B 细胞 ALL） 是最常见的儿童癌症。尽管总体治愈率很高，但复发性 B 细胞 ALL 仍然是儿童癌症相关死亡的主要原因。在儿童新诊断的标准风险（由美国国家癌症研究所定义）B 细胞急性淋巴细胞白血病的治疗中加入双特异性 T 细胞接合分子 blinatumomab（一种抗 CD19 和抗 CD3 单链分子）可能会改善结局。方法 我们进行了一项 3 期试验，涉及新诊断的标准风险 B 细胞 ALL 儿童，这些儿童具有平均或高度的复发风险。患者被随机分配接受单独化疗或化疗加两个非序贯 28 天周期的 blinatumomab。主要终点是无病生存期。结果数据和安全性监测委员会审查了第一次中期疗效分析的结果，其中包括 1440 名接受随机分组的患者 （722 名单独化疗和 718 名 blinatumomab 联合化疗） 并建议提前终止随机化。中位随访 2.5 年时，blinatumomab 联合化疗组估计的 3 年无病生存率 （±SE） 为 96.0±1.2%，单独化疗为 87.9±2.1%（限制性平均生存时间差异，72 天;95% 置信区间，36 至 108;P<0.001 通过分层对数秩检验）。在平均复发风险患者中，估计的 3 年无病生存率为 blinatumomab 联合化疗组 97.5±1.3%，单独化疗组 90.2±2.3%;在复发风险高的人群中，相应的值为 94.1±2.5% 和 84.8±3.8%。 细胞因子释放综合征、癫痫发作和 3 级或更高级别的脓毒症在 blinatumomab 周期中很少见，但在分配接受 blinatumomab 和化疗的具有平均复发风险的患者中，非致死性脓毒症和导管相关感染的总体发生率显著高于分配接受单独化疗的患者。结论 对于新诊断的中等或高风险复发风险的儿童标准风险 B 细胞 ALL 患者，在联合化疗中加入 blinatumomab 可显著提高无病生存率。（由美国国立卫生研究院（National Institutes of Health）和其他机构资助;AALL1731 ClinicalTrials.gov 号，NCT03914625.）。