Editor's Note: At the 2026 European Hematology Association (EHA) Annual Meeting, Professor Martin Schrappe, on behalf of the AIEOP-BFM consortium, announced the latest analysis data from the Phase III randomized controlled clinical trial AIEOP-BFM ALL 2017. This study aimed to explore the clinical benefits of using the bispecific antibody Blinatumomab to completely replace two cycles of high-intensity toxic chemotherapy in newly diagnosed pediatric and adolescent patients with high-risk (HR) B-cell acute lymphoblastic leukemia (B-ALL). The results showed that this strategy not only significantly improved the event-free survival (EFS) rate of patients but also substantially reduced treatment-related toxicity and transplant-related mortality.01 Research Background and AIEOP-BFM 2017 Trial Design
Although the treatment of pediatric B-ALL has made significant progress, patients in the high-risk (HR) group still face high relapse risks and severe chemotherapy toxicity. The COG 1731 study published in 2024 showed that adding two cycles of Blinatumomab in standard-risk (NCI-SR) patients significantly improved prognosis. Based on this, the AIEOP-BFM study group initiated an exploration targeting high-risk pediatric patients at an earlier time point. The AIEOP-BFM ALL 2017 trial enrolled approximately 5,000 patients (as of September 2023), with 21% classified into the high-risk group. Criteria for high-risk classification included: failure to achieve complete remission on day 33 (non-remission), presence of unfavorable genetic alterations (such as KMT2A rearrangement, etc.), poor integrated assessment of genetics and treatment response (PCR-MRD), and specific age groups. After completing HR-1 consolidation therapy, eligible pediatric patients were randomized into either the experimental group or the control group: • Control Group: Received two cycles of standard high-dose intensity combination chemotherapy (HR-2 and HR-3 blocks). HR-2 was based on dexamethasone, high-dose methotrexate, anthracyclines, and ifosfamide; HR-3 was based on dexamethasone, high-dose cytarabine (Ara-C), etoposide (VP-16), L-asparaginase, and intrathecal methotrexate. • Experimental Group: Two cycles of Blinatumomab (15 μg/m²/d, intravenous infusion) completely replaced the aforementioned HR-2 and HR-3 chemotherapy. If patients in the experimental group showed poor MRD response after two weeks of Blinatumomab treatment, they were allowed to switch back to chemotherapy.
02 Efficacy Breakthrough: Significant Improvement in EFS and Substantial Decrease in Recurrence Risk
The results of the third interim analysis were encouraging. The study reached its primary endpoint, significantly improving Event-Free Survival (EFS) after randomization. • EFS Benefit: The EFS of patients in the experimental group reached 83%, an improvement of more than 10% compared to the control group (HR=0.51, 95% CI data to be released upon further follow-up). This survival data has never been achieved in previous treatments for high-risk pediatric ALL. • Comparison of Relapse Rates: The risk of relapse in the experimental group was reduced by nearly 50%. Particularly in terms of isolated central nervous system (CNS) relapse, only 1 case was observed in the experimental group, compared to 9 cases in the control group. Professor Schrappe pointed out that although the experimental group received two additional doses of intrathecal methotrexate, this is insufficient to fully explain such a significant difference; Blinatumomab may more effectively prevent the dissemination of leukemia cells to the CNS by clearing minimal residual disease (MRD). • Overall Survival (OS): Currently, there is no significant difference in OS between the two groups, mainly attributed to the widespread use of Blinatumomab in salvage therapy for relapsed patients in the control group.
03 MRD Dynamics: Deeper Molecular Remission
Minimal Residual Disease (MRD) is a core indicator for predicting the prognosis of ALL. The study compared the dynamic changes of MRD after the first cycle of treatment: • After completing the first cycle of treatment (HR-2 or the first cycle of Blinatumomab), the proportion of patients in the experimental group achieving MRD negativity or a significant decrease reached 77%, significantly higher than the 46% in the control group. • Subgroup Benefit: Regardless of whether MRD was positive (about 1/3 of patients) or negative (about 2/3 of patients) before randomization, the experimental group showed consistent survival benefits. Especially for MRD-positive patients, the efficacy benefit in the experimental group (79% vs 58%) was significantly superior to the chemotherapy group.
04 Safety Overview: Significant Reduction in Fatal Toxicity and Transplant-Related Mortality
Safety is one of the most noted highlights of this study. Blinatumomab demonstrated an excellent safety profile, successfully achieving “reduced toxicity and increased efficacy.” • Treatment-Related Mortality: During complete remission (CR), the number of deaths in the experimental group was 10, significantly lower than the 18 in the control group. • Transplant-Related Mortality (TRM): The most statistically significant finding was that for high-risk pediatric patients requiring hematopoietic stem cell transplantation, the number of deaths after transplantation in the experimental group was only 2, compared to 12 in the control group. This indicates that using Blinatumomab to replace chemotherapy before surgery improved the patients’ functional status and organ reserves, reducing the risk of lethal complications during subsequent transplantation. • Adverse Event (AE) Characteristics: o Neurotoxicity: The incidence of neurotoxicity in the experimental group was 12%, higher than that in the control group (rarely occurring in the chemotherapy group), requiring close monitoring. o Routine Toxicity: Common side effects of chemotherapy such as severe infection, pancreatitis, allergic reactions, and severe mucositis were significantly reduced in the experimental group. o Life-threatening AEs: During the randomized treatment phase, no life-threatening severe AEs occurred in the experimental group, while they occurred frequently in the control group.
05 Conclusion and Outlook: Initiating the “De-chemotherapy” Era for High-Risk B-ALL
Professor Martin Schrappe concluded that the AIEOP-BFM ALL 2017 study confirmed that in the post-induction remission treatment of pediatric and adolescent high-risk B-ALL, replacing high-intensity combination chemotherapy with Blinatumomab not only significantly improves EFS but also substantially reduces multiple risks including relapse, treatment-related mortality, and transplant-related mortality. The success of this study marks a major transformation in the treatment model for pediatric leukemia. In the subsequent discussion, Professor Schrappe mentioned that based on the current excellent data, the research group plans to launch a new study starting from September 2025, attempting to further reduce the chemotherapy proportion by 50%, striving to enable more ALL treatments to be completed in outpatient settings. This aims to maintain cure rates while maximizing the quality of life for pediatric patients.
