"Upfront Use of Blinatumomab in Adolescents and Adults With Philadelphia Chromosome: Negative B-cell Acute Lymphoblastic Leukemia: A Systematic Review and Proportional Meta-Analysis".

Blinatumomab, a CD3×CD19 bispecific T-cell engager, has demonstrated efficacy in relapsed/refractory (R/R) and measurable residual disease-positive (MRD+) B-cell acute lymphoblastic leukemia (B-ALL), as well as in frontline consolidation following the ECOG-ACRIN E1910 trial that established its regulatory approval in this setting. However, its optimal timing during induction and across combined treatment phases in newly diagnosed Philadelphia chromosome-negative (Ph-) B-ALL remains under investigation. We performed a systematic review and proportional meta-analysis following PRISMA guidelines to evaluate clinical outcomes of blinatumomab-based frontline regimens in adolescents and adults with Ph- B-ALL. Studies were stratified by treatment phase (induction, consolidation, or both). Primary endpoints were complete remission (CR) and MRD negativity; secondary endpoints included 3-year overall survival (OS) and safety. Thirteen studies (n = 827) met inclusion criteria. The pooled CR rate among studies using blinatumomab during induction was 77% (95% CI 70-83%). The overall pooled MRD negativity rate across all phases was 88% (95% CI 82-92%), with comparable results across subgroups. The pooled 3-year OS was 67% (95% CI 55-78%), though survival differed by patient fitness and chemotherapy backbone. Grade ≥3 cytokinerelease syndrome and neurotoxicity occurred in <10% of patients. Frontline blinatumomab regimens achieve high complete remission (77%) and deep MRD negativity (88%) with manageable toxicity in Ph- B-ALL. Variations in OS appear driven by patient heterogeneity and concurrent chemotherapy intensity rather than blinatumomab timing. Future studies should refine its integration within targeted and genomically defined strategies, particularly for high-risk subsets such as Ph-like and KMT2A-rearranged B-ALL.