During a presentation at the ASH Annual Meeting, researchers said recent findings definitively establish that adding blinatumomab to chemotherapy significantly improves disease-free survival (DFS) in newly diagnosed pediatric standard-risk B-cell acute lymphoblastic leukemia (SR B-ALL). The combination therapy brought patients with both average and high risk of mortality more in line with outcomes seen in patients with favorable risk profiles.
“Relapsed ALL is a leading cause of pediatric cancer mortality, and about half of relapses occur in SR B-ALL,” wrote the authors, led by Rachel E. Rau, MD, of Seattle Children’s Hospital and the University of Washington. “The addition of blinatumomab represents a major breakthrough and is a new treatment standard, with implications for children with newly diagnosed B-ALL.”
Their phase III trial assessed whether the addition of two non-sequential cycles of blinatumomab (15 mg/m2/day IV continuous infusion for 28 days) to chemotherapy would improve DFS in these children. They assignedpatients aged 1–9 years to one of three risk groups based on tumor genetics, central nervous system status, and minimal residual disease (MRD). At the time of data cutoff for this analysis, the study had 1,440 evaluable patients with a median age of 4.3 years and a median follow-up of 2.5 years. Of those, the study team randomized 722 patients and 718 to blinatumomab.
Three-year DFS (± standard error) was 96.0 ± 1.2% for patients randomized to blinatumomab versus 87.9 ± 2.1% for controls. For standard-risk patients, three-year DFS with blinatumomab was 97.5 ± 1.3% versus 90.2 ± 2.3%. For high-risk patients, the results were 94.1 ± 2.5% versus 84.8 ± 3.8%. The results substantially exceeded expectations and led to recommendations for early termination of randomization.
Six deaths occurred among patients who were in remission, all of whom were standard risk, and none of the deaths occurred during blinatumomab cycles. The drug was well tolerated, with only 0.3% of first courses associated with grade 3 or higher cytokine release syndrome and 0.7% associated with seizures.
https://ash.confex.com/ash/2024/webprogram/Paper207450.html
Reference
Rau RE, Gupta S, Kairalla JA, et al. Blinatumomab added to chemotherapy improves disease-free survival in newly diagnosed NCI standard risk pediatric b-acute lymphoblastic leukemia: results from the randomized Children’s Oncology Group study AALL1731. Abstract #1. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7–10, 2024; San Diego, California.
