The addition of blinatumomab to standard chemotherapy improved disease-free survival in children with standard-risk B-cell acute lymphoblastic leukemia, reducing relapse rates by 8.5 percentage points (from 11.8% to 3.3%), according to a recent study.
In the phase 3 trial, researchers evaluated the addition of blinatumomab to standard chemotherapy for children with newly diagnosed standard-risk B-cell acute lymphoblastic leukemia (B-cell ALL). The trial aimed to determine whether two cycles of blinatumomab, a bispecific T-cell engager, could improve disease-free survival (DFS) in children with an average or high risk of relapse.
Published in The New England Journal of Medicine, the study enrolled 1,440 patients (median age 4.3 years, 52.6% boys, 25.8% Hispanic, 5.6% non-Hispanic Black), who were randomly assigned to receive either chemotherapy alone or chemotherapy plus blinatumomab. The primary endpoint was DFS. Based on significant improvements seen in the first interim analysis, the data and safety monitoring committee recommended early termination of randomization.
The estimated 3-year DFS rate was 96.0% (±1.2%) in the blinatumomab group, compared to 87.9% (±2.1%) in the chemotherapy-alone group (P<0.001) at a median follow-up of 2.5 years. Overall survival rates were 98.4% (±0.9%) with blinatumomab and chemotherapy versus 97.1% (±1.1%) with chemotherapy alone. The improvement in DFS was observed in both risk subgroups. Among those with an average risk of relapse, the 3-year DFS was 97.5% (±1.3%) with blinatumomab and chemotherapy, versus 90.2% (±2.3%) with chemotherapy alone. For patients with high relapse risk, the 3-year DFS was 94.1% (±2.5%) in the blinatumomab group and 84.8% (±3.8%) in the chemotherapy-alone group.
The addition of blinatumomab significantly reduced bone marrow relapse. The estimated 3-year cumulative incidence was 1.5% (±0.5%) with blinatumomab and chemotherapy compared to 7.7% (±1.3%) with chemotherapy alone. Among patients who relapsed, all those tested (69 of 75) were CD19-positive. There was no significant difference in isolated central nervous system relapse between groups.
Regarding adverse events, patients with average risk receiving blinatumomab experienced higher rates of grade 3 or higher sepsis and catheter-related infections (14.8% vs. 5.1%, P<0.001) during subsequent treatment cycles. However, they showed lower rates of allergic reactions (2.8% vs. 7.2%, P=0.01), and the incidence of severe infections during blinatumomab cycles remained low.
This study concluded that adding blinatumomab to standard chemotherapy significantly improves DFS in children with standard-risk B-cell ALL, particularly by reducing bone marrow relapse, without substantially increasing the risk of severe infections during blinatumomab cycles. These findings support the potential use of blinatumomab as an adjunct to chemotherapy in treating pediatric patients with B-cell ALL. Longer-term follow-up is needed to confirm that the improvements in outcomes persist over time.
Full disclosures can be found in the published study.
