FDA Approval Summary: Blinatumomab for the Treatment of B-Cell Precursor Acute Lymphoblastic Leukemia in the Consolidation Phase of Multiphase Chemotherapy.

On June 14, 2024, the FDA approved blinatumomab (BLINCYTO; Amgen, Inc.) in the consolidation phase of treatment for CD19-positive, Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (BCP ALL). The FDA reviewed results from three randomized trials using blinatumomab in consolidation: Study E1910 (adult patients with newly diagnosed BCP ALL without minimal residual disease), Study 20120215 (pediatric patients with high-risk BCP ALL in first relapse), and Study AALL1331 (pediatric and young adult patients with BCP ALL in first relapse). Study E1910 demonstrated a significant improvement in overall survival (OS) when comparing alternating blinatumomab and chemotherapy cycles versus chemotherapy cycles alone [HR = 0.42; 95% confidence interval (CI), 0.24-0.75; P = 0.003]. In Study 20120215, the efficacy of blinatumomab as an alternative to a third cycle of chemotherapy was primarily supported by descriptive analyses of the secondary endpoint of OS (HR = 0.35; 95% CI, 0.17-0.7) and a post hoc analysis of relapse-free survival (HR = 0.38; 95% CI, 0.22-0.66). AALL1331 did not meet its primary objectives for the randomizations in the high/intermediate-risk arm comparing blinatumomab versus chemotherapy or in the low-risk arm comparing blinatumomab cycles and chemotherapy cycles versus chemotherapy cycles alone. A meta-analysis of OS performed using the above studies and the infant study NL59901.078.17 was consistent with a treatment effect of blinatumomab during consolidation. The safety profile of blinatumomab cycles was consistent with previous studies. The benefit of blinatumomab during the consolidation phase of therapy is consistent across line of therapy (newly diagnosed vs. relapsed) and patient age (adult vs. pediatric).