PDF(Pubmed)
Abstract：
The bispecific T cell-binding antibody blinatumomab (CD19/CD3) is widely and successfully used for the treatment of children with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Here, we report the efficacy of a single course of blinatumomab instead of consolidation chemotherapy to eliminate minimal residual disease (MRD) and maintain stable MRD-negativity in children with primary BCP-ALL.Between February 2020 and November 2022, 177 children with non-high-risk BCP-ALL were enrolled in the ALL-MB 2019 pilot study (NCT04723342). Patients received the usual risk-adapted induction therapy according to the ALL-MB 2015 protocol. Those who achieved a complete remission at the end of induction (EOI) received treatment with blinatumomab immediately after induction at a dose of 5 μg/m2/day for 7 days and 21 days at a dose of 15 μg/m2/day, followed by 12 months of maintenance therapy. MRD was measured using multicolor flow cytometry (MFC) at the EOI, then immediately after blinatumomab treatment, and then four times during maintenance therapy at 3-month intervals.All 177 patients successfully completed induction therapy and achieved a complete hematological remission. In 174 of these, MFC-MRD was measured at the EOI. 143 patients (82.2%) were MFC-MRD negative and the remaining 31 patients had varying degrees of MFC-MRD positivity.MFC-MRD was assessed in all 176 patients who completed the blinatumomab course. With one exception, all patients achieved MFC-MRD negativity after blinatumomab, regardless of the MFC-MRD score at EOI. One adolescent girl with high MFC-MRD positivity at EOI remained MFC-MRD positive. Of 175 patients who had completed 6 months of maintenance therapy, MFC-MRD data were available for 156 children. Of these, 155 (99.4%) were MFC-MRD negative. Only one boy with t(12;21) (p13;q22)/ETV6::RUNX1 became MFC-MRD positive again. The remaining 174 children had completed the entire therapy. MFC-MRD was examined in 154 of them, and 153 were MFC-MRD negative. A girl with hypodiploid BCP-ALL showed a reappearance of MFC-MRD with subsequent relapse.In summary, a single 28-day course of blinatumomab immediately after induction, followed by 12 months of maintenance therapy, is highly effective in achieving MRD-negativity in children with newly diagnosed non-high risk BCP-ALL and maintaining MRD-negative remission at least during the treatment period.
摘要：
双特异性T细胞结合抗体blinatumomab（CD19/CD3）被广泛且成功地用于治疗患有复发性或难治性B细胞前体急性淋巴细胞白血病（BCP-ALL）的儿童。这里,我们报道了在原发性BCP-ALL患儿中,单疗程博纳单抗替代巩固化疗消除微小残留病(MRD)和维持稳定MRD阴性的疗效.在2020年2月至2022年11月之间，177名非高危BCP-ALL儿童被纳入ALL-MB2019试点研究（NCT04723342）。根据ALL-MB2015方案，患者接受了通常的风险适应诱导治疗。那些在诱导结束时（EOI）达到完全缓解的人在诱导后立即以5μg/m2/天的剂量接受blinatumomab治疗7天和21天，剂量为15μg/m2/天，随后进行12个月的维持治疗。使用多色流式细胞术(MFC)在EOI测量MRD，然后在Blinatumomab治疗后立即，然后在维持治疗期间以3个月的间隔进行四次。所有177例患者均成功完成诱导治疗，并达到完全血液学缓解。在其中的174个中，MFC-MRD在EOI处测量。143例(82.2%)患者MFC-MRD阴性,其余31例患者均有不同程度的MFC-MRD阳性。对所有176名完成blinatumomab疗程的患者进行MFC-MRD评估。除了一个例外,所有患者在blinatumomab后均达到MFC-MRD阴性，无论MFC-MRD得分在EOI。一名在EOI中MFC-MRD阳性的青春期女孩保持MFC-MRD阳性。在175名完成6个月维持治疗的患者中，MFC-MRD数据可用于156名儿童。其中,155例(99.4%)为MFC-MRD阴性。只有一个男孩t(12;21)(p13;q22)/ETV6::RUNX1再次变为MFC-MRD阳性。其余174名儿童完成了整个治疗。MFC-MRD在其中154人中进行了检查，153例MFC-MRD阴性。患有亚二倍体BCP-ALL的女孩表现出MFC-MRD的再次出现，随后复发。总之,诱导后立即进行为期28天的单疗程，随后进行12个月的维持治疗，在新诊断的非高风险BCP-ALL儿童中实现MRD阴性并至少在治疗期间维持MRD阴性缓解方面非常有效。
