婴幼儿中KMT2A重排的急性淋巴细胞白血病（ALL）是一种侵袭性疾病，三年事件自由生存率不到40％。大多数复发发生在治疗期间，其中三分之二在诊断后的一年内发生，90％在诊断后的两年内发生。尽管化疗强度增加，近几十年来的结果并没有改善。我们对连结CD19的双特异性 T 細胞聯合剂分子 blinatumomab在婴幼儿KMT2A重排的ALL的安全性和有效性进行了研究。给予30名年龄小于1岁的新诊断KMT2A-rearranged ALL患者用于Interfant-06试验的化疗方案，并加入一次感应后的blinatumomab （每平方米体表面积15μg；28天连续输注）。主要终点是临床相关的毒副作用，即任何毒副作用可能或明确归因于blinatumomab并导致永久停止blinatumomab或死亡。用聚合酶链反应测量最小残余病（MRD）。收集有关不良事件的数据。与Interfant-06试验的历史对照数据进行比较。中位随访时间为26.3个月（范围3.9至48.2）。所有30名患者都接受了完整的blinatumomab课程。未发生符合主要终点定义的毒副作用。报告了10例严重不良事件（发热[4个事件]，感染[4个]，高血压[1个]和呕吐[1个]）。毒副作用概况与老年患者报告的相一致。在blinatumomab输注后，28名患者（93％）要么是MRD阴性（16名患者），要么在MRD水平很低（<5×10-4 [<5个白血病细胞/ 10,000个正常细胞]，12名患者）。所有继续化疗的患者在进一步治疗期间均成为MRD阴性。我们的研究中2年无病生存率为81.6％（95％置信区间 [CI]，60.8至92.0），而Interfant-06试验的相应值为49.4％（95％ CI，42.5至56.0）；总生存率的相应值为93.3％（95％ CI，75.9至98.3）和65.8％（95％ CI，58.9至71.8）。向Interfant-06化疗方案中添加blinatumomab似乎在新诊断的KMT2A重排的ALL婴儿中是安全的，并具有高的疗效水平，与Interfant-06试验的历史对照相比。（受 Princess Máxima Center 基金会和其他机构赞助；EudraCT号码，2016-004674-17。）版权所有© 2023 Massachusetts Medical Society。

KMT2A-rearranged acute lymphoblastic leukemia (ALL) in infants is an aggressive disease with 3-year event-free survival below 40%. Most relapses occur during treatment, with two thirds occurring within 1 year and 90% within 2 years after diagnosis. Outcomes have not improved in recent decades despite intensification of chemotherapy.We studied the safety and efficacy of blinatumomab, a bispecific T-cell engager molecule targeting CD19, in infants with KMT2A-rearranged ALL. Thirty patients younger than 1 year of age with newly diagnosed KMT2A-rearranged ALL were given the chemotherapy used in the Interfant-06 trial with the addition of one postinduction course of blinatumomab (15 μg per square meter of body-surface area per day; 28-day continuous infusion). The primary end point was clinically relevant toxic effects, defined as any toxic effect that was possibly or definitely attributable to blinatumomab and resulted in permanent discontinuation of blinatumomab or death. Minimal residual disease (MRD) was measured by polymerase chain reaction. Data on adverse events were collected. Outcome data were compared with historical control data from the Interfant-06 trial.The median follow-up was 26.3 months (range, 3.9 to 48.2). All 30 patients received the full course of blinatumomab. No toxic effects meeting the definition of the primary end point occurred. Ten serious adverse events were reported (fever [4 events], infection [4], hypertension [1], and vomiting [1]). The toxic-effects profile was consistent with that reported in older patients. A total of 28 patients (93%) either were MRD-negative (16 patients) or had low levels of MRD (<5×10-4 [i.e., <5 leukemic cells per 10,000 normal cells], 12 patients) after the blinatumomab infusion. All the patients who continued chemotherapy became MRD-negative during further treatment. Two-year disease-free survival was 81.6% in our study (95% confidence interval [CI], 60.8 to 92.0), as compared with 49.4% (95% CI, 42.5 to 56.0) in the Interfant-06 trial; the corresponding values for overall survival were 93.3% (95% CI, 75.9 to 98.3) and 65.8% (95% CI, 58.9 to 71.8).Blinatumomab added to Interfant-06 chemotherapy appeared to be safe and had a high level of efficacy in infants with newly diagnosed KMT2A-rearranged ALL as compared with historical controls from the Interfant-06 trial. (Funded by the Princess Máxima Center Foundation and others; EudraCT number, 2016-004674-17.).Copyright © 2023 Massachusetts Medical Society.