Blinatumomab Demonstrates MRD Eradication in MRD-Positive/Chemotherapy-Delayed Pediatric B-ALL and High Response in Relapsed/Refractory Cases: A Multicenter Cohort Study

Na Zhang¹Wenting Hu²Yunpeng Dai³Jian Wang⁴Lijun Qu⁴Dan Wang¹Bingju Liu³Jingbo Shao¹Shuhong Shen^2*Hui Jiang^1*

• ¹Department of Hematology and Oncology, Shanghai Children's Hospital, Shanghai, Shanghai Municipality, China
• ²Department of Hematology and Oncology, Shanghai Children's Medical Center, Shanghai, China
• ³Department of Pediatric Hematology/Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
• ⁴department of Hematology and Oncology, Anhui Children's Hospital, Hefei, China

Background: Blinatumomab, a bispecific T-cell engager towards CD3+ and CD19+, promotes T cell–mediated cytotoxicity against B-cell precursor acute lymphoblastic leukemia (B-ALL). While its efficacy is established in relapsed/refractory (R/R) disease, its role as preemptive therapy for minimal residual disease (MRD)–positive patients or those experiencing chemotherapy delays remain undefined. Predictors of treatment failure also require further investigation. Methods: In this multicenter retrospective study, 105 patients who received blinatumomab were enrolled. Among them, 30 had R/R ALL, 21 were in complete remission (CR) with MRD positivity (CR-MRDpos), and 54 experienced chemotherapy delays. In total, 11 children were in R/R status and 40 were in CR-MRDpos before treatment. Patients were subsequently bridged to stem cell transplantation, CAR-T, or protocol continuation. Treatment response was analyzed across CR-MRDpos, R/R, and CR with MRD negative (CR-MRDneg) patients. Immune reconstitution profiles (T-cell subsets, cytokine dynamics), cytogenetic markers, and clinical outcomes were assessed to identify predictors of treatment resistance. Results: CR rate was 81.8% in R/R and 82.5% in CR-MRDpos (P = 1.000). Of 74 courses with CR-MRDneg, 73 remained MRD-negative during treatment. Univariate analysis revealed poor cytogenetics (P = 0.0001), CD19+ B-cell loss (P = 0.046), and BCR/ABL1 positivity (P = 0.002) as poor response. Cox regression model analysis demonstrated high MRD (P = 0.014), BCR/ABL1 (P = 0.065), and poor cytogenetic (P = 0.025) as independent risk factors. Blinatumomab significantly increased CD3+ T cells [0.96 (0.03–3.79) to 1.13 (0.26–7.74) ×109/L, P = 0.016], along with CD4+ [0.35 (0.01–1.39) to 0.47 (0.07–2.94) ×109/L] and CD8+ T cells [0.41 (0.01–2.39) to 0.56 (0.07–6.07) ×109/L] (P = 0.005 and P = 0.006, respectively).The 1-year event-free survival for CR-MRDneg, CR-MRDpos, and R/R patients was 97.8%  2.2%, 86.7%  6.2%, and 73.3%  8.1% (P = 0.001), while overall survival was 97.8%  2.2%, 100%, and 93.3%  4.6% (P = 0.029). Conclusions: Blinatumomab effectively clears MRD as preemptive therapy and served as a bridging strategy during chemotherapy delays in B-ALL, maintaining high response rates in R/R cases.