Blinatumomab Substitution Improves EFS in Pediatric High-Risk B-ALL

Replacing 2 highly intensive conventional chemotherapy courses (HR-2’, HR-3’) with blinatumomab (Blincyto) demonstrated safety and significantly improved event-free survival (EFS) among pediatric patients with high-risk B-cell acute lymphoblastic leukemia (B-ALL), according to a presentation on data from the phase 3 AIEOP-BFM ALL 2017 trial (NCT03643276) at the 2026 European Hematology Association (EHA) Congress.¹

At 4 years, the EFS rates were 83% with blinatumomab vs 70.3% with HR-2’, HR-3’. Among patients with minimal residual disease (MRD) positivity before the randomized treatment phase in the experimental (n = 110) and control arms (n = 105), the 4-year EFS rates were 79.1% and 58.3%, respectively. Regarding those with MRD-negative status before randomization in the experimental (n = 243) and control arms (n = 220), the respective EFS rates were 86.4% vs 77.1% at 4 years.

Of note, the 4-year cumulative incidence of relapse (CIR) rates were 11.8% in the experimental arm vs 21.4% in the control arm, and the rates of cumulative incidence of death were 2.9% vs 5.9%, respectively. The 4-year rates of overall survival (OS) were 93.6% and 91.0% in each respective group. Among 110 patients in the blinatumomab arm with MRD-positive status after an initial course of chemotherapy (HR-1’), MRD decreased in 76.9% of patients after the first cycle of blinatumomab; this corresponding rate was 45.8% after HR-2’ among 105 patients in the control arm with MRD positivity following HR-1’.

“The replacement of 2 highly intensive chemotherapy courses by 2 cycles of blinatumomab given [intravenously] improved the [EFS] significantly in [patients with] high-risk B-ALL. Both systemic- and central nervous system [CNS]–related relapses have been reduced by replacing chemotherapy in favor of introducing blinatumomab,” study investigator Martin Schrappe, MD, PhD, from University Medical Center Schleswig-Holstein, Campus Kiel, Pediatric Hematology and Oncology, ALL-BFM Study Group, Kiel, Germany, stated in his presentation of the data. “Patients with very high-risk features who have an indication for allogeneic transplant have a better outcome due to the reduced transplant-related mortality. The toxicity profile of blinatumomab in high-risk patients is very favorable, but the neurological toxicity needs to be monitored carefully.”

After administering induction, consolidation, and 1 intensive chemotherapy course to patients with B-ALL, investigators of the phase 3 trial randomly assigned 709 eligible patients with high-risk characteristics to receive 2 cycles of blinatumomab at 15 μg/m² per day for 28 days (n = 358) or 2 additional chemotherapy blocks: HR-2’, HR-3’ (n = 351). The study’s primary question was determining whether EFS could be improved by at least 10% from the time of randomization with blinatumomab. Secondary objectives included reducing treatment-related life-threatening complications and mortality during the intensified consolidation phase of high-risk therapy and the proportion of patients with MRD response to blinatumomab vs the HR-2’ block in the control arm.

Patients with newly diagnosed acute lymphoblastic leukemia, newly diagnosed mixed phenotype acute leukemia, or newly diagnosed acute undifferentiated leukemia were eligible for enrollment on the trial.² For the specific analysis presented at EHA, patients with high-risk disease were defined as those with no complete remission on day 33, positivity for KMT2A::AFF1, positivity for TCF3::HLF1, or a hypodiploidy of fewer than 45 chromosomes. Being younger than 1 year old with any KMT2A rearrangement was another criterion for high-risk status.

Across the experimental and control arms, most patients were 10 to 17 years old (33.2% vs 33.9%), met NCI high-risk criteria (54.2% vs 52.4%), and had CNS1 involvement (75.7% vs 72.7%). Of note, relapses occurred in 8.7% of the experimental arm and 16.2% of the control arm, with 0.3% vs 2.5% experiencing CNS-isolated relapses.

During the randomized phase of the trial, 23.9% of patients in the blinatumomab arm had infections compared with 69.4% of those in the chemotherapy arm (P <.001), with 12.0% vs 3.2% having nervous system disorders (P <.001). Other toxicities showing significant differences between arms included pancreatitis (0.3% vs 2.1%; P = .03) and serious mucositis (0.3% vs 10.0%; P <.001). The most significant life-threatening adverse effects (AEs) during this phase were infections; no patients in the blinatumomab arm experienced any events compared with 3.2% in the chemotherapy arm (P <.001).

Following the randomized phase, life-threatening AEs were reported in 6.4% of the experimental arm vs 7.3% of the control arm, which mostly consisted of bacterial sepsis (3.2% vs 2.7%). Fatal AEs occurred in 2.5% and 2.3% of patients in each arm, the most common of which was bacterial sepsis (1.0% vs 0.8%).

References

1. Schrappe M, Locatelli F, Valsecchi MG, et al. Replacement of high dose combination chemotherapy with blinatumomab in newly diagnosed pediatric high-risk B-cell ALL improves efficacy and safety in the randomized phase 3 AIEOP-BFM ALL 2017 trial. Presented at the 2026 European Hematology Association Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S103.
2. Treatment protocol for children and adolescents with acute lymphoblastic leukemia - AIEOP-BFM ALL 2017. ClinicalTrials.gov. Updated April 6, 2025. Accessed June 13, 2026. https://tinyurl.com/mr3casph