Blinatumomab Cuts Toxicity, Boosts Survival in High-Risk ALL

Substituting 2 cycles of blinatumomab (Blincyto; Amgen), a bispecific T-cell engager, for 2 cycles of highly toxic chemotherapy nearly doubled 4-year event-free survival (EFS) among children with newly diagnosed high-risk B-cell acute lymphoblastic leukemia (ALL), while cutting treatment-related infections by more than half. The findings, from the phase 3 AIEOP-BFM ALL 2017 trial (NCT03643276) were published recently in The New England Journal of Medicine.¹

These results add first-line evidence to a growing immunotherapy replacement strategy for pediatric ALL, a disease group in which cure rates are high but treatment-related toxicity remains a persistent burden for survivors. EFS is the trial’s primary end point.

The trial’s consortium screened 5068 children with newly diagnosed leukemia across sites in Australia, Austria, Czech Republic, Germany, Israel, Italy, Slovakia, and Switzerland between July 15, 2018, and August 31, 2023. Of the 84.7% (n = 4293) patients shown to have Philadelphia-chromosome–positive B-cell ALL, 21.0% (n = 902) met the study’s definition of high-risk disease, which the investigators defined by the presence of minimal residual disease (MRD), presence of fusion genes KMT2A::AFF1 and TCF::HLF, hypodiploidy, and the IKZF1plus genetic profile.

Ultimately, 709 patients were randomly assigned to receive two 28-day cycles of blinatumomab after consolidation chemotherapy (n = 358) or 2 additional cycles of intensive chemotherapy (n = 351). Demographic characteristics were similar between the groups, with most patients aged 1 to 9 years (59.5% of the treatment cohort and 59.8% of the control cohort), having a white blood cell count of less than 20,000/μl (57.3% and 58.1%, respectively), and classified as standard risk per National Cancer Institute criteria (45.8% and 47.6%). Median (IQR) follow-up was 2.9 (2.0-4.1) years.

What the Survival and Relapse Data Show

At the planned interim analysis, which used follow-up data updated on February 1, 2025, 4-year EFS was 83.0% (95% CI, 7.4%-87.4%) in the blinatumomab group vs 70.3% (95% CI, 63.8%-75.9%; P = .0002) in the control group. This translates to a 49% reduction in mortality risk (HR, 0.51; 95% CI, 0.35-0.73).

Thirty-one patients in the blinatumomab group relapsed vs 57 in the control group, for a 4-year relapse incidence of 11.8% (95% CI, 7.9%-16.5%) compared with 21.4% (95% CI, 16.1%-27.3%), respectively. Death during first complete remission was also less common with blinatumomab than chemotherapy (2.9% vs 5.9%), a gap the study authors attributed largely to fewer fatal complications from allogeneic hematopoietic stem cell transplantation in the blinatumomab group. Corresponding 4-year overall survival rates were 93.6% and 91.0%.

“We have shown that blinatumomab group can safely replace chemotherapy as first-line treatment of pediatric high-risk B-cell ALL,” the study authors wrote.

Infection related to the trial treatment occurred in 23.9% of patients in the blinatumomab group compared with 69.4% of patients in the control group (P < .001). Life-threatening adverse events were reported in 2 patients who received blinatumomab, 1 of which was fatal, vs 16 patients who received chemotherapy. Neurotoxic events were more frequent with blinatumomab than chemotherapy (12.2% vs 3.2%; P < .001), most often seizures of at least grade 2 (4.6% and 0.9%; P = .001) and other neurotoxic events (7.6% and 1.8%; P < .001); these also occurred more often in children 10 years and older, at 19.0% and 5.4%, compared with children aged 1 to 9 years, at 9.3% and 2.4%.

“Certain neurotoxic events related to blinatumomab, such as seizures, may be presented with the use of prophylactic medication,” the authors noted, adding that regular immunoglobulin monitoring may be warranted given the B-cell aplasia that follows treatment.

Are There Treatment Implications?

The present findings build on previous research into early-line use of blinatumomab in pediatric ALL, including to reduce MRD before transplant and as a substitute for chemotherapy in children with relapsed disease.² They also follow the Children’s Oncology Group AALL1731 trial (NCT03914625), which found that adding blinatumomab to standard chemotherapy instead of replacing chemotherapy improved 3-year disease-free survival to 96.0% from 87.9% in standard-risk pediatric B-cell ALL, with a pronounced benefit among Hispanic children.³

For payers and health systems, the shift toward frontline immunotherapy in high-risk pediatric ALL carries implications beyond survival curves: fewer infection-related hospitalizations and transplant-related death could reduce acute care utilization, even as clinicians weight the added need for neurotoxicity monitoring and immunoglobulin replacement. The study authors noted that the optimal timing of blinatumomab relative to chemotherapy remains undefined and that its benefit extended even to MRD-negative patients, potentially suggesting residual leukemia below the detection threshold may still respond to the therapy.

References

1. Schrappe M, Locatelli F, Valsecchi MF, et al; AIEOP-BFM ALL 2017 Consortium. Blinatumomab for replacing chemotherapy in pediatric acute lymphoblastic leukemia. N Engl J Med. 2026;395(11):1075-1089. doi:10.1056/NEJMoa2604166
2. McCormick B, Schrappe M. Blinatumomab improves outcomes, toxicity in high-risk pediatric ALL: Martin Schrappe, MD, PhD. AJMC^®. June 13, 2026. Accessed September 18, 2026. https://www.ajmc.com/view/blinatumomab-improves-outcomes-toxicity-in-high-risk-pediatric-all-martin-schrappe-md-phd
3. Caffrey M. Adding blinatumomab to chemo boosts survival in common pediatric leukemia, results show. AJMC. December 7, 2024. Accessed September 18, 2026. https://www.ajmc.com/view/adding-blinatumomab-to-chemo-boosts-survival-in-common-pediatric-leukemia-results-show