Blinatumomab has emerged as a promising component of first-line therapy for acute B-cell precursor lymphoblastic leukemia (BCP-ALL), bolstering treatment efficacy. To mitigate CD19 selection pressure and reduce the incidence of blinatumomab-associated toxicities, pre-treatment chemotherapy is recommended before administering blinatumomab. From September 2022 to December 2023, we conducted a single-arm, multicenter, phase 2 trial (NCT05557110) in newly diagnosed Philadelphia chromosome-negative BCP-ALL (Ph-negative BCP-ALL) patients. Participants received induction treatment with reduced-dose chemotherapy (RDC), comprising idarubicin, vindesine, and dexamethasone over 7 days, followed by 2 weeks of blinatumomab. Those failing to achieve composite complete remission (CRc) received an additional 2 weeks of blinatumomab. The primary endpoint was the CRc rate post initial induction treatment. Of the 35 enrolled patients, 33 (94%) achieved CRc after 2 weeks of blinatumomab, with 30 (86%) achieving measurable residual disease (MRD) negativity. Two patients extended blinatumomab to 4 weeks. With either 2 or 4 weeks of blinatumomab treatment, all patients achieved CR (35/35) and 89% (31/35) were MRD negativity. The median time to CR was 22 days. Immune effector cell-associated neurotoxicity syndrome was limited (14%, all grade 1). Non-hematological adverse events of grade 3 or higher included pneumonia (17%), sepsis (6%), and cytokine release syndrome (9%). With a median follow-up of 11.5 months, estimated 1-year overall survival and 1-year progression-free survival rates were 97.1% and 82.2%, respectively. These findings affirm that RDC followed by blinatumomab is an effective and well-tolerated induction regimen for newly diagnosed Ph-negative BCP-ALL, supporting a shift towards less intensive and more targeted therapeutic approaches. Trial registration: https://www.clinicaltrials.Gov . Identifier NCT05557110.

中文翻译：

---

减少剂量化疗和 blinatumomab 作为新诊断 Ph 阴性 B 细胞前体急性淋巴细胞白血病的诱导治疗：一项 2 期试验


博纳吐单抗已成为急性 B 细胞前体淋巴细胞白血病 (BCP-ALL) 一线治疗的有前景的成分，可增强治疗效果。为了减轻 CD19 选择压力并降低 blinatumomab 相关毒性的发生率，建议在给予 blinatumomab 之前进行预处理化疗。 2022年9月至2023年12月，我们对新诊断的费城染色体阴性BCP-ALL（Ph阴性BCP-ALL）患者进行了一项单臂、多中心、2期试验（NCT05557110）。参与者接受了为期 7 天的减剂量化疗 (RDC) 诱导治疗，其中包括伊达比星、长春地辛和地塞米松，然后接受 2 周的博纳吐单抗治疗。未能实现复合完全缓解 (CRc) 的患者额外接受 2 周的 blinatumomab 治疗。主要终点是初始诱导治疗后的 CRc 率。在 35 名入组患者中，33 名 (94%) 患者在接受 blinatumomab 治疗 2 周后达到 CRc，其中 30 名 (86%) 患者达到可测量残留病 (MRD) 阴性。两名患者将 blinatumomab 的治疗时间延长至 4 周。通过 blinatumomab 治疗 2 周或 4 周，所有患者均达到 CR (35/35)，并且 89% (31/35) 的 MRD 呈阴性。达到 CR 的中位时间为 22 天。免疫效应细胞相关神经毒性综合征有限（14%，均为 1 级）。 3 级或以上的非血液学不良事件包括肺炎（17%）、败血症（6%）和细胞因子释放综合征（9%）。中位随访时间为 11.5 个月，预计 1 年总生存率和 1 年无进展生存率分别为 97.1% 和 82.2%。 这些发现证实，对于新诊断的 Ph 阴性 BCP-ALL，RDC 继之以 blinatumomab 是一种有效且耐受性良好的诱导方案，支持向强度较低、更有针对性的治疗方法的转变。试验注册：https://www.clinicaltrials.Gov。标识符 NCT05557110。