Blincyto + chemo boosts survival in pediatric B-ALL

The data are from a Phase III study (AALL1731) conducted by the Children's Oncology Group. The results were simultaneously published in the New England Journal of Medicine and will be presented during the plenary session on Sunday, Dec. 8, at the 66^th American Society of Hematology (ASH) Annual Meeting & Exposition in San Diego.

The AALL1731 study was a Phase III randomized trial to determine if two non-sequential cycles of Blincyto  added to chemotherapy improved disease-free survival (DFS) in children with newly diagnosed pediatric National Cancer Institute (NCI) standard risk (SR) B-cell acute lymphoblastic leukemia (B-ALL). The study enrolled 4,264 newly diagnosed NCI SR B-ALL patients, of whom 2,334 were risk stratified at the end of induction therapy as either SR-Average or SR-High. At the first planned interim efficacy analysis (data cutoff June 30, 2024), 1,440 of the eligible and evaluable patients had been randomized. The AALL1731 study was designed and conducted independently from (the pharma) industry. The Cancer Therapy Evaluation Program (CTEP) of the NCI sponsored the trial and provided funding to the Children's Oncology Group to conduct the study. In addition, Amgen provided Blincyto and support through an NCI Cooperative Research and Development Agreement.

Based on the results of the first pre-specified interim analysis for efficacy, the study met its primary endpoint of DFS and study randomization was terminated early based on the recommendation from the data and safety monitoring committee due to the benefit observed in the Blincyto  arm compared to the chemotherapy-only arm. Overall, the 3-year DFS was 96.0% for patients treated with chemotherapy plus Blincyto  compared to 87.9% for those treated with only chemotherapy. The hazard ratio (HR) was 0.39 [95% confidence interval (CI) 0.24-0.64], indicating a 61% reduction in the risk of disease relapse, secondary malignant neoplasm or remission death with Blincyto . At 3 years, more patients remained alive and cancer free when treated with Blincyto plus chemotherapy compared to chemotherapy alone.

The addition of Blincyto  to chemotherapy in standard risk patients resulted in outcomes similar to those previously achieved in only the most favorable pediatric risk subsets. Among SR-Average patients, 3-year DFS was 97.5% for patients treated with Blincyto  compared to 90.2% for those treated with only chemotherapy (HR 0.33, CI 0.15-0.69). For SR-High patients, 3-year DFS was 94.1% for those treated with Blincyto O compared to 84.8% for those treated with only chemotherapy (HR 0.45, 95% CI 0.24-0.85).

Safety results are consistent with the known profile of Blincyto, which has already demonstrated a positive balance of benefits and risks, with only 0.3% of first courses associated with Grade 3+ cytokine release syndrome (CRS) and 0.7% with seizures. A higher risk of infections was observed in the Blincyto arm.

These results provide the first evidence supporting Blincyto for use in the consolidation phase in newly diagnosed pediatric Philadelphia chromosome-negative (Ph-) B-ALL patients. This groundbreaking first-in-class Bispecific T-cell Engager (BiTE) therapy is now backed by additional evidence reinforcing its role in redefining a standard of care for both adult and pediatric patients, starting from one month old, regardless of measurable residual disease (MRD) status. The findings further establish Blincyto as a versatile first-line consolidation therapy across all ages and treatment backbones. 

"Over the last decade, BLINCYTO has reshaped the treatment landscape for B-ALL, offering a critical lifeline for thousands of adult and pediatric patients," said Dr. Jay Bradner, executive VP of R&D and CSO at Amgen. "These powerful new data leave us little doubt about the profound impact of this medicine for a large number of children affected by this disease. We are grateful to the Children's Oncology Group, along with the patients, families and clinical teams, for their dedication and partnership in advancing this critical study to improve the lives of children with cancer."

"The AALL1731 study results are truly practice-changing, further solidifying blinatumomab's role as the standard of care for a large number of children with B-ALL," said Dr. Sumit Gupta, co-chairman of the Children's Oncology Group AALL1731 study and oncologist and clinician investigator, Division of Haematology/Oncology at The Hospital for Sick Children and associate professor of pediatrics at the University of Toronto. "These breakthrough data showing a significant improvement in disease-free survival are poised to bring substantial clinical value to children with newly diagnosed B-ALL."

"Relapsed ALL remains a major cause of pediatric cancer mortality, with nearly half of the relapses occurring in children with standard-risk B-ALL," said Dr. Rachel E. Rau, co-chairwoman of the Children's Oncology Group AALL1731 study, pediatric hematologist-oncologist at Seattle Children's Hospital and associate professor of pediatrics at the University of Washington. "These findings underscore the progress made with blinatumomab in preventing relapse and support its role as a critical addition to current therapeutic strategies."

See Citation- Gupta S, Rau RE.,  Kairalla JA, Rabin KR  et al. "Blinatumomab in Standard-Risk B-Cell Acute Lymphoblastic Leukemia in Children".  N Engl J Med 2024 Published online7 December  DOI: 10.1056/NEJMoa2411680