Replacing two blocks of chemotherapy with two blocks of the bispecific antibody blinatumomab significantly improved event-free survival in children with high-risk B-cell acute lymphoblastic leukemia (B-ALL), according to findings from the randomized, phase 3 AIEOP-BFM ALL 2017 trial.

At 4 years, event-free survival was 12.7 percentage points higher with blinatumomab than with chemotherapy, and relapses were about half as likely.

The event-free survival outcome in these high-risk patients receiving blinatumomab “has never been reached before,” said lead author Martin Schrappe, MD, PhD, professor of pediatric hematology and oncology, University Hospital Schleswig-Holstein, Kiel, Germany, during his presentation at the European Hematology Association (EHA) 2026 Congress. And “we did not expect such a reduction in relapse.”

Although about 80% of pediatric patients with ALL are considered cured, children with high-risk B-ALL continue to have inferior survival outcomes than standard-risk patients, largely due to treatment-resistant disease and toxicities associated with intensive chemotherapy, explained pediatric oncologist Ching-Hon Pui, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, who was not involved with the study.

These patients often experience reduced quality of life during treatment due to acute toxicities and may have long-term complications and late effects that persist after therapy is completed, Pui said.

Blinatumomab, a type of targeted immunotherapy, is FDA approved for various high-risk patient populations with B-ALL, including those with CD19-positive disease in first or second complete remission, relapsed or refractory disease as well as Philadelphia chromosome-negative B-ALL in the consolidation phase of multiphase chemotherapy.

The study initially enrolled 5068 patients from 2018 to September 2023 and focused on 709 (92.3%) of 768 eligible patients with high-risk B-ALL. Nearly 60% of patients were aged 1-9 years, about one third were aged 10-17 years, and a small proportion were younger than 1 year. The primary objective was an improvement in event-free survival of at least 10% from the time of randomization, Schrappe explained.

At 4 years, event-free survival was 83.0% with blinatumomab vs 70.3% with chemotherapy. Additionally, relapses were much less likely in the blinatumomab group (8.7% vs 16.2%).

“Most striking was the reduction in isolated CNS [central nervous system] relapses with only one in the experimental arm compared to nine in the control arm,” Schrappe said.

Overall survival was high in both groups, exceeding 90% at 4 years (93.6% with blinatumomab vs 91.0% with chemotherapy). Although fewer patients in the blinatumomab arm died during follow-up (2.9% vs 5.9%), the similarly high overall survival rates were “not a surprise,” Schrappe said, “because patients who were in the chemo group all received immunotherapy with blinatumomab at the time of relapse.”

Among transplanted patients, nonrelapse mortality was lower with blinatumomab — 2.5% (2 of 79 patients) vs 16% with chemotherapy (12 of 73 patients).

Blinatumomab carries a black box warning for cytokine release syndrome and neurologic toxicities, including immune effector cell-associated neurotoxicity syndrome.

Neurologic toxicity with blinatumomab warrants careful monitoring, but all other toxicity categories in the study occurred more frequently in the chemotherapy arm, Schrappe said.

During the randomized phase, infections and life-threatening infections were more common in the chemotherapy group (69.4% vs 23.9% and 3.2% vs none), while nervous system disorders and life-threatening nervous system disorders were more common in the blinatumomab arm (12.0% vs 3.2% and 0.3% vs none). After the randomized phase, life-threatening adverse events were more common in the chemotherapy group (7.3% vs 6.4%), though bacterial sepsis was slightly more common in the blinatumomab arm (3.2% vs 2.7%).

Schrappe also noted that the more favorable minimal residual disease response of blinatumomab-treated patients “is an early indicator of improved outcome.” He also noted that patients with very high-risk features who undergo allogeneic hematopoietic stem cell transplantation appear to have better outcomes because of reduced transplant-related mortality.

Overall, Pui said the study is “well-designed” and “provides strong evidence supporting the incorporation of blinatumomab into frontline treatment for children with newly diagnosed high-risk B-ALL.”

However, he cautioned that “in this study, blinatumomab replaced specific chemotherapy blocks within a broader, multiagent treatment program rather than serving as a standalone therapy.”

University Hospital Schleswig-Holstein funded the study, and Amgen provided blinatumomab. Disclosure information for the authors was not provided. Pui had no disclosures.