Replacing two cycles of highly toxic, high-dose combination chemotherapy with two cycles of blinatumomab as first-line (1L) treatment significantly improves outcomes including 4-year event-free survival (EFS) and reduces adverse events (AEs) in paediatric patients with high-risk B-cell acute lymphoblastic leukaemia (B-ALL), results of the phase III AIEOP-BFM 2017 trial have shown.
The international, investigator-initiated, intergroup, multicentre, open-label, randomized trial included 5,068 paediatric patients with newly diagnosed Philadelphia chromosome–negative ALL recruited from July 2018 to August 2023 (for B-ALL) or March 2024 (for T-cell ALL). Among 4,293 patients with B-ALL, 902 (21 percent) had high-risk characteristics. After consolidation chemotherapy with or without bortezomib, 709 of 768 patients (92.3 percent) with high-risk B-ALL were randomized to receive two cycles of blinatumomab (n=358) or cycles 2 and 3 of high-dose combination chemotherapy (control group; n=351). [Schrappe M, et al, EHA 2026, abstract S103; N Engl J Med 2026;395:1075-1089]
“The primary study question was whether 4-year EFS could be improved by at least 10 percent in the blinatumomab vs control group,” said Professor Martin Schrappe of the University Medical Center Schleswig-Holstein, Campus Kiel, Germany.
Secondary endpoints included overall survival (OS), cumulative incidence of death during complete remission (CR), and cumulative incidence of relapse. “We also assessed minimal residual disease [MRD] response after cycle 1 of blinatumomab vs cycle 2 of chemotherapy,” Schrappe added.
Unprecedented 4-year EFS
After a median follow-up from randomization of 2.9 years, estimated 4-year EFS rate was 83 percent in the blinatumomab group vs 70.3 percent in the control group (p=0.0002) (estimated hazard ratio, 0.51; 95 percent confidence interval, 0.35–0.73).
“An 83 percent 4-year EFS rate has never been reached before in these high-risk patients,” remarked Schrappe.
Among patients with MRD-positive status before the randomized treatment phase (n=110 and 105 in the blinatumomab and control group, respectively), 4-year EFS rate was 79.1 vs 58.3 percent with blinatumomab vs chemotherapy. Those with MRD-negative status before randomization (n=243 and 220, respectively) also benefited from blinatumomab, with a 4-year EFS rate of 86.4 vs 77.1 percent.
Reduced relapse, improved MRD response
“The cumulative incidence of relapse at 4 years was halved in the blinatumomab vs control group, at 11.8 vs 21.4 percent. What was most striking was the reduction in isolated central nervous system relapse, which occurred in only one patient in the blinatumomab group vs nine patients in the control group,” Schrappe reported. “We did not expect such a reduction in relapse.”
At 4 years, the estimated cumulative incidence of death during first CR was 2.9 vs 5.9 percent, while OS rate was 93.6 vs 91 percent. “The similar OS was not a surprise, as all patients in the control group who relapsed received blinatumomab,” said Schrappe.
Among patients who were MRD-positive before randomization, reduction in MRD level was achieved in 76.9 vs 45.8 percent after the first cycle of randomized treatment with blinatumomab vs chemotherapy. “The more favourable MRD response to blinatumomab is an early indicator of improved outcome,” Schrappe noted.
Favourable toxicity profile
“Blinatumomab demonstrated a very favourable toxicity profile in these high-risk patients, although neurotoxicity requires careful monitoring,” said Schrappe.
Most AEs, including infection (23.9 vs 69.4 percent; p<0.001) and life-threatening AEs (0.5 vs 4.7 percent), were less frequent with blinatumomab vs chemotherapy, although neurotoxic effects were reported in 12 vs 3.2 percent of patients (p<0.001).