Blinatumomab versus chemotherapy in pediatric B-ALL: A meta-analysis of randomized trials in relapsed and high-risk frontline disease

Abstract

BACKGROUND: B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric cancer, comprising almost 25 % of childhood malignancies. Despite advances in chemotherapy, relapse remains a major cause of treatment failure, particularly in high-risk patients. Blinatumomab, a CD19-directed bispecific T-cell engager, approved for relapsed/refractory and measurable residual disease (MRD)-positive B-ALL, but its benefit in pediatric patients at increased risk of relapse remains uncertain. OBJECTIVE: To evaluate whether adding blinatumomab to chemotherapy improves survival and MRD outcomes in pediatric patients with relapsed/refractory or high-risk frontline B-ALL. METHODS: We searched PubMed, EMBASE, and Cochrane Library through March 2025, following PRISMA 2020 guidelines. Randomized controlled trials (RCTs) evaluating blinatumomab versus chemotherapy in pediatric B-ALL patients at increased risk of relapse. Primary outcomes were disease-free survival (DFS). Overall survival (OS), MRD, and adverse effects were also assessed. Risk ratios (RRs) with 95 % confidence intervals (CIs) were pooled using random-effects models. RESULTS: Four RCTs involving 2,011 patients were included. Blinatumomab significantly improved DFS (RR: 0.63, 95 % CI: 0.47-0.83; P = 0.001) and OS (RR: 0.62, 95 % CI: 0.47-0.84; P = 0.002). No statistically significant improvement was observed in MRD clearance (RR: 1.21, 95 % CI: 0.56-2.62; P = 0.62). Adverse event rates were similar between groups (RR: 1.00, 95 % CI: 0.57-1.75; P = 0.99), although heterogeneity was high. CONCLUSION: This meta-analysis suggests that adding Blinatumomab to chemotherapy improves survival in pediatric relapsed/refractory B-ALL and selected high risk frontline populations. However, limited frontline evidence and variability in MRD and toxicity reporting warrant further standardized pediatric studies.