TOPLINE

A phase 3 trial found that replacing two cycles of intensive chemotherapy with two cycles of blinatumomab significantly improved event-free survival (EFS) among children with newly diagnosed high-risk B-cell acute lymphoblastic leukemia (ALL). The estimated 4-year EFS rates were 83.0% among patients who received blinatumomab and 70.3% among those who continued receiving additional chemotherapy cycles. Blinatumomab was also associated with substantially reduced toxic effects, including treatment-related infections and life-threatening adverse events.

METHODOLOGY

• Despite advances in risk-stratified therapy, relapse and treatment toxicity remain common among children with high-risk B-cell ALL. Blinatumomab, a CD19-directed bispecific T-cell engager, has shown benefit in both relapsed and standard-risk disease settings.
• To evaluate whether two cycles of blinatumomab could safely replace two cycles of traditional chemotherapy, researchers conducted a phase 3 trial involving 709 children younger than 18 years with newly diagnosed high-risk B-cell ALL across eight countries.
• After consolidation and one cycle of intensive chemotherapy, the patients were randomly assigned to receive either two 28-day cycles of blinatumomab (15 µg/m2/d, capped at 28 µg; n = 358; blinatumomab group) or two cycles of intensive chemotherapy (n = 351; control group).
• High-risk criteria included the absence of complete remission on day 33 after the initiation of treatment, the presence of specific genetic features (KMT2A::AFF1 fusion, TCF3::HLF fusion, hypodiploidy, or IKZF1plus), and minimal residual disease (MRD) positivity at specified thresholds.
• The primary outcome was EFS, and the duration of EFS was measured as the interval from randomization to resistance to protocol treatment, relapse, second cancer, or death from any cause. The secondary outcomes were overall survival, the cumulative incidence of death during complete remission, and the cumulative incidence of relapse. Patients were followed up for a median duration of 2.9 years after randomization.

TAKEAWAY

• Overall, the 4-year EFS was significantly higher in the blinatumomab group than in the control group (83% vs 70.3%; hazard ratio, 0.51), with estimated event rates of 0.046 and 0.090 cases per person-year, respectively. The 4-year overall survival did not differ significantly between the two groups (93.6% vs 91.0%).
• Relapse occurred less frequently in the blinatumomab group than in the control group; the 4-year cumulative incidence of relapse was 11.8% in the blinatumomab group vs 21.4% in the control group. The occurrence of death during the first complete remission at 4 years was less common in the blinatumomab group (2.9% vs 5.9%), a gap driven mainly by fewer transplant-related deaths in the blinatumomab group than in the control group (2.5% vs 16.4%).
• Among patients with MRD-positive status after initial treatment, MRD clearance occurred in 69.2% after the first cycle of blinatumomab vs 32.3% after the second cycle of intensive chemotherapy.
• Treatment-related infections (23.9% vs 69.4%) and life-threatening adverse events (0.5% vs 4.7%) were substantially less frequent in the blinatumomab group than in the control group, whereas neurotoxic events were significantly more frequent in the blinatumomab group (12.0% vs 3.2%). Grade ≥ 2 cytokine-release syndrome occurred in 1.1% of patients receiving blinatumomab.

IN PRACTICE

″These findings provide a basis for evaluating immunotherapy-based replacement strategies across broader B-cell ALL risk groups,″ the study authors wrote.

″In the current trial, the size of the effect of blinatumomab on event-free survival (hazard ratio, 0.51) mirrored the results of trials in other populations, which further establishes blinatumomab as a new standard of care in B-cell ALL,″ Regina M. Myers, MD, and Stephen P. Hunger, MD, both of the Department of Pediatrics, Children's Hospital of Philadelphia, pointed out in an accompanying editorial.

SOURCE

The study, led by Martin Schrappe, MD, Christian Albrechts University Kiel and University Hospital Schleswig-Holstein, Campus Kiel in Kiel, Germany, was published online in the New England Journal of Medicine.

LIMITATIONS

The ideal time to initiate blinatumomab has not yet been established. Subgroup analyses were post hoc and involved small patient numbers, warranting cautious interpretation. The pathogenesis of neurotoxic events and the optimal duration of immunoglobulin monitoring after blinatumomab remain undefined.

DISCLOSURES

The study was supported by Deutsche Krebshilfe, Associazione Italiana Ricerca contro il Cancro, the Fondazione Maria Letizia Verga and Fondazione Tettamanti, and other organizations. Amgen provided blinatumomab free of charge but had no role in trial design or data evaluation. Several authors reported receiving grants, consulting fees, or research support from pharmaceutical companies, including Amgen, AbbVie, Becton, Dickinson and Company, and others, with few authors being employees or shareholders of Amgen. Full disclosures are reported in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.