The addition of blinatumomab (Blincyto) to standard chemotherapy significantly improves three-year disease-free survival (DFS) in pediatric patients newly diagnosed with standard-risk B-cell acute lymphoblastic leukemia (B-ALL). The findings, from the Children’s Oncology Group Study AALL1731, suggest a new standard of care for this patient population.
The study, presented at the 2024 American Society of Hematology (ASH) Annual Meeting, showed a marked increase in DFS rates with the addition of blinatumomab. At a median follow-up of 2.5 years, the three-year DFS rate in the overall population was 96% with blinatumomab plus chemotherapy, compared to 87.9% with chemotherapy alone (HR, 0.39; 95% CI, 0.24-0.64; P < .0001).
Improved Outcomes Across Risk Groups
The benefits of blinatumomab were observed across different risk groups within the standard-risk category. In the standard-risk average population, the three-year DFS rate was 97.5% with the addition of blinatumomab, compared to 90.2% with chemotherapy alone (HR, 0.33; P = .0019). Similarly, in the standard-risk high population, the respective rates were 94.1% and 84.8% (HR, 0.45; P = .0126).
According to Dr. Rachel E. Rau, lead study author and associate professor of pediatrics at the University of Washington and Seattle Children’s Hospital, the improvement in DFS was primarily due to a significant reduction in bone marrow relapses. The study did not find a similar reduction in isolated central nervous system (CNS) relapses, which aligns with blinatumomab’s known limited activity in the CNS.
Study Design and Patient Population
The AALL1731 trial enrolled patients aged 1 to under 10 years with newly diagnosed National Cancer Institute (NCI) standard-risk B-ALL. Patients with CNS3 involvement, testicular leukemia, or those pretreated with steroids were excluded. Participants started therapy with a standard three-drug induction regimen and were then assigned to risk stratification groups based on their expected NCI risk of relapse.
Patients with standard-risk favorable disease, standard-risk average disease with undetectable immunoglobulin minimal residual disease (MRD), and standard-risk high disease with MRD levels between 0.1% and 1% were not eligible for randomization.
Safety Profile and Adverse Events
The safety profile of blinatumomab in this study was consistent with its known safety profile. Common target toxicities included cytokine release syndrome (CRS), seizures, and encephalopathy. In the standard-risk average population, higher rates of grade 3 or higher infectious toxicities were observed in the blinatumomab arm, including febrile neutropenia, sepsis, and catheter-related infections.
Impact on Treatment Paradigm
These findings suggest that adding blinatumomab to chemotherapy could become a new standard of care for most patients with NCI standard-risk B-ALL. Dr. Rau concluded that the results demonstrate a significant step forward in the treatment of this disease, offering improved outcomes for a large number of children.
According to Dr. Sumit Gupta, co-chair of the Children's Oncology Group AALL1731 study, these data are practice-changing and solidify blinatumomab's role as the standard of care for a large number of children with B-ALL. He added that the breakthrough data showing a significant improvement in disease-free survival are poised to bring substantial clinical value to children with newly diagnosed B-ALL.
