Editor's Note:The 66th Annual Meeting of the American Society of Hematology (ASH) was held from December 7 to 10, 2024, in San Diego, USA. This global event brought together leading experts in hematology to discuss the latest advancements in the field. At the meeting, the team led by Dr. Ruidong Zhang from Beijing Children’s Hospital，Capital Medical University presented significant findings (Abstract O312) on the treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL), providing fresh insights and possibilities for future therapies. Hematology Frontier invited Dr. Peijing Qi, the study's lead investigator, to provide an in-depth analysis of the research and its implications for clinical practice.

Study Overview

Efficacy and Safety of Adding Blinatumomab to First-Line Treatment for Chinese Children with B-Cell Acute Lymphoblastic Leukemia

01. Rationale for Incorporating Blinatumomab into First-Line Treatment

Hematology Frontier: B-ALL is the most common type of leukemia in children, with chemotherapy as the primary treatment. However, some children struggle with chemotherapy intolerance, and intermediate- and high-risk patients often have suboptimal prognoses. Why did you consider adding blinatumomab to first-line treatment for these patients? How do you expect it to improve treatment outcomes?

• Dr. Peijing Qi:

B-ALL is one of the most prevalent malignant tumors in children, with a consistently high incidence, posing a serious threat to pediatric health. Despite a cure rate of approximately 90%, challenges remain. Many children face significant hurdles during treatment, including chemotherapy intolerance, pancreatitis, thrombosis, and severe infections. These complications place a heavy burden on both patients and their families, underscoring the urgent need for more effective solutions.

Unfortunately, 10% to 15% of children experience relapse, which is devastating for patients and their families. In light of this, our team, led by Dr. Ruidong Zhang, has been committed to exploring more effective therapies to further improve clinical outcomes.

In the past two years, blinatumomab has been approved for treating pediatric relapsed or refractory B-ALL. Clinical observations and evaluations have demonstrated its excellent safety profile and effectiveness in reducing minimal residual disease (MRD) levels. This makes blinatumomab a promising new option, particularly for children who cannot tolerate chemotherapy.

In this study, we included patients who were chemotherapy-intolerant or at intermediate and high risk. By introducing immunotherapy as a bridge or transitional treatment, we aimed to help these patients continue chemotherapy or transition smoothly to transplantation. This approach offers new hope for improving treatment outcomes in this challenging population.

02. Key Findings and Their Clinical Implications

Hematology Frontier: The study results showed impressive remission indicators following blinatumomab treatment, with notable two-year EFS and OS data. What do you consider the most surprising findings, and what is their significance for guiding clinical practice?

• Dr. Peijing Qi:

The study had a follow-up period of 26.8 months, with a median time from diagnosis to the administration of blinatumomab of 10.8 months. The results were highly encouraging. The two-year event-free survival (EFS) rate reached an astonishing 97.8%, and the two-year overall survival (OS) rate was 100%. Among the 90 patients enrolled, only two experienced relapse: one with the TCF3-PBX1 mutation and the other with MLL-AF4.

To further evaluate these results, we applied propensity score matching (PSM) to compare this cohort with 90 historical control patients treated under the CCLG-B-ALL-2018 protocol. The blinatumomab group demonstrated significantly improved two-year EFS and OS rates.

Subgroup analysis further revealed that high-risk children receiving blinatumomab had significantly higher two-year EFS and OS rates compared to the control group, particularly those with minimal residual disease (MRD) levels above 0.1% at the end of induction therapy.

These findings suggest that incorporating blinatumomab into the treatment of high-risk populations, especially those with high MRD levels post-induction, could offer substantial survival benefits. However, these conclusions are preliminary and based on the current dataset. Rigorous future clinical studies are necessary to validate the safety and efficacy of this approach.

03. Future Prospects of Blinatumomab in Pediatric B-ALL Treatment

Hematology Frontier: Based on the study’s findings, what is your perspective on the future role of blinatumomab in pediatric B-ALL treatment? Are there plans for further research, such as combining it with other therapies to enhance efficacy or reduce toxicity?

• Dr. Peijing Qi:

Considering the wealth of clinical research data both domestically and internationally, along with past clinical experience, blinatumomab shows immense potential across various settings in pediatric acute lymphoblastic leukemia treatment. It has demonstrated efficacy not only in relapsed and refractory cases but also in first-line treatment.

Building on this potential, the Chinese Children’s Leukemia Group (CCLG) has launched a multicenter, prospective study to optimize the application of blinatumomab. This study, part of the CCLG-2018-ALL supplemental protocol, aims to moderately reduce the intensity of induction therapy for intermediate- and high-risk patients. Additionally, it incorporates 2–4 weeks of blinatumomab into subsequent treatments.

This research is currently progressing actively and aims to further validate and refine this innovative therapeutic strategy to maximize efficacy while minimizing toxicity.

About Dr. Ruidong Zhang

Dr. Ruidong Zhang is a leading expert in pediatric leukemia and serves as a senior physician, doctoral supervisor, and director of the Leukemia Department at Beijing Children’s Hospital. His numerous roles include Deputy Director of the Leukemia Group under the National Health Commission and Vice Chair of the Pediatric Hematology Group of the Chinese Medical Association. He has contributed extensively to pediatric leukemia research and serves as an editor for multiple academic journals.

About Dr. Peijing Qi

Dr. Peijing Qi is an associate chief physician specializing in pediatric leukemia at Beijing Children’s Hospital. With her expertise and involvement in groundbreaking studies, she continues to advance the field of pediatric hematology, focusing on innovative treatments for acute lymphoblastic leukemia.