Impact of Pretransplant Blinatumomab on Post-Transplant Outcomes in B Cell Acute Lymphoblastic Leukemia: A Systematic Review and Meta-Analysis.

B cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematological malignancy that often requires allogeneic hematopoietic cell transplant (HCT) for long-term remission. Outcomes after HCT are affected by pretransplant disease burden, especially measurable residual disease (MRD) status. Blinatumomab, a CD19/CD3 bispecific T cell engager, has shown effectiveness in eliminating MRD in patients with B-ALL. Its effect on HCT outcomes is uncertain. To determine the impact of pretransplant blinatumomab on B-ALL outcomes after HCT. We performed a systematic review and meta-analysis of prospective and retrospective adult B-ALL studies comparing blinatumomab with chemotherapy before HCT. The protocol was registered in PROSPERO (CRD42024582654). The primary outcome was cumulative incidence of relapse (CIR). Secondary outcomes included overall survival (OS), relapse-free survival (RFS), nonrelapse mortality (NRM), and incidence of graft-versus-host disease (GVHD). Hazard ratios (HRs) were pooled using a random-effects restricted maximum likelihood model with a Hartung-Knapp adjustment. Risk of bias and certainty of evidence were assessed using RoB 2 or ROBINS-I V2 and the GRADE approach. Seven studies met the inclusion criteria (1 randomized trial and 6 retrospective cohorts). We included 1068 patients, of whom 172 received blinatumomab. Pooled HRs comparing blinatumomab with chemotherapy were: 0.67 (95% confidence interval (95% CI): 0.22 to 2.01; prediction interval (PI) 0.09 to 4.96) for CIR, 0.82 (95% CI: 0.44 to 1.53; PI: 0.44 to 1.52) for OS, 0.63 (95% CI: 0.22 to 1.77; PI: 0.16 to 2.40) for RFS, and 0.84 (95% CI: 0.36 to 2.00; PI: 0.34 to 2.07) for NRM, with low to moderate heterogeneity. Blinatumomab was associated with a reduction in grade III to IV acute GVHD (HR: 0.50, 95% CI: 0.28 to 0.89; PI: 0.00 to 141.43). Across available studies, pretransplant blinatumomab use had no statistically significant impact on OS, CIR, RFS, or NRM after HCT in patients with B-ALL; however, effect estimates were highly imprecise. A reduction in the incidence of grade III to IV acute GVHD should be interpreted cautiously. Prospective studies adequately powered with consistent MRD assays, standardized transplant platforms, and uniform remission status cohorts are needed to clarify the role of pretransplant blinatumomab.