Blinatumomab vs. chemotherapy in pediatrics B-cell ALL: A meta-analysis of randomized controlled trials

Abstract Background: B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric cancer, comprising up to 25% of childhood malignancies. Although standard risk patients have more than 85% survival with chemotherapy, relapses and treatment related toxicity remain major concerns. Blinatumomab, a bispecific T-cell engager targeting CD19, is FDA-approved for relapsed/refractory and MRD-positive B-ALL, but its role in frontline therapy for standard risk pediatric patients is unclear. Objective: Given the prognostic value of minimal residual disease (MRD), this meta-analysis reviews randomized controlled trials (RCTs) to assess whether adding Blinatumomab to chemotherapy improves survival and MRD outcomes in pediatric B-ALL, focusing on relapsed and high-risk populations. Methods: We searched PubMed, EMBASE, and Cochrane Library through March 2025, following PRISMA 2020 guidelines. Randomized controlled trials (RCTs) evaluating blinatumomab versus standard chemotherapy in pediatric patients with B-ALL were included. Primary outcome was disease-free survival (DFS). Overall survival (OS), minimal residual disease (MRD) and adverse effects were also assessed. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Results: After primary and secondary screening four RCTs including 2,011 pediatric patients met inclusion criteria. Of these, 1,004 received blinatumomab and 1,007 received standard chemotherapy. Blinatumomab significantly improved DFS with the reduction of disease recurrence up to 37% approximately (RR: 0.63, 95% CI: 0.47–0.83; P = 0.001) and OS with decrease in mortality up to 38% approximately (RR: 0.62, 95% CI: 0.47–0.84; P = 0.002). No statistically significant improvement was observed in MRD clearance (RR: 2.53, 95% CI: 0.32–19.85; P = 0.38). Adverse event rates were similar between groups (RR: 1.00, 95% CI: 0.57–1.75; P = 0.99), though heterogeneity for these outcomes was high. Conclusion: This meta-analysis supports adding Blinatumomab to chemotherapy for improved survival in pediatric relapsed/refractory B-ALL. Its focus on pediatric RCTs enhances relevance, but variability in MRD response and adverse event reporting limits conclusions on safety. Standardized MRD and toxicity assessments are needed. Findings should be interpreted cautiously due to patient and study heterogeneity, underscoring the need for harmonized pediatric research.