This randomized phase 3 trial compared blinatumomab, a bispecific monoclonal antibody, with standard chemotherapy in adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). The primary endpoint was overall survival. Of the 405 patients enrolled, 376 received at least one dose of treatment. Blinatumomab significantly improved overall survival compared to chemotherapy (median 7.7 months vs. 4.0 months; hazard ratio, 0.71; P = 0.01). Remission rates within 12 weeks were higher with blinatumomab (complete remission with full hematologic recovery: 34% vs. 16%; complete remission with full, partial, or incomplete hematologic recovery: 44% vs. 25%). Event-free survival was also better with blinatumomab (6-month estimates, 31% vs. 12%). Adverse events were common in both groups, with higher rates of serious events in the chemotherapy group. The trial was stopped early due to the significant survival benefit of blinatumomab. This study demonstrates that blinatumomab provides a significant survival advantage over chemotherapy in adults with relapsed or refractory B-cell precursor ALL.This randomized phase 3 trial compared blinatumomab, a bispecific monoclonal antibody, with standard chemotherapy in adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). The primary endpoint was overall survival. Of the 405 patients enrolled, 376 received at least one dose of treatment. Blinatumomab significantly improved overall survival compared to chemotherapy (median 7.7 months vs. 4.0 months; hazard ratio, 0.71; P = 0.01). Remission rates within 12 weeks were higher with blinatumomab (complete remission with full hematologic recovery: 34% vs. 16%; complete remission with full, partial, or incomplete hematologic recovery: 44% vs. 25%). Event-free survival was also better with blinatumomab (6-month estimates, 31% vs. 12%). Adverse events were common in both groups, with higher rates of serious events in the chemotherapy group. The trial was stopped early due to the significant survival benefit of blinatumomab. This study demonstrates that blinatumomab provides a significant survival advantage over chemotherapy in adults with relapsed or refractory B-cell precursor ALL.