Blinatumomab Boosts Survival in Pediatric ALL, but Faces Delivery Hurdles

While adding blinatumomab to chemotherapy provides a sustained and significant survival benefit for children with higher-risk B-cell acute lymphoblastic leukemia (B-ALL), there are complex requirements for this standard of care, which can create substantial hurdles in outpatient delivery, according to research presented at the American Society of Hematology 2025 annual meeting, held in Orlando, Florida.¹

Blinatumomab Improves Survival and Eliminates Risk Factors

Longer-term follow-up from the Children’s Oncology Group (COG) Trial AALL1731 reinforced the fundamental shift in pediatric ALL treatment by demonstrating that the improved outcomes associated with blinatumomab persist.

The trial enrolled children between the ages of 1 and 9 who were newly diagnosed with National Cancer Institute standard risk (SR) B-ALL without BCR::ABL1 fusion or testicular or central nervous system disease. A total of 1444 patients were randomized, and 133 patients were censored.

The trial had 4 arms. Arms A and B included patients with an average risk of relapse and detectable indeterminate end-of-induction minimal residual disease (MRD). Arm A received chemotherapy only, while Arm B received chemotherapy plus blinatumomab. In arms C and D, patients were at higher risk of relapse with an end-of-consolidation MRD of < 0.1%. Arm C received high-intensity chemotherapy, while Arm D received chemotherapy plus blinatumomab.

After a median follow-up of 3.5 years, the 4-year disease-free survival (DFS; ± standard error) for patients who received blinatumomab arms was 94.8% (± 1.5%) compared with 86.9% (± 2.2%) for patients who only received chemotherapy. The 4-year cumulative incidence of relapse (CIR) was 4.4% (± 0.9%) for blinatumomab arms versus 12.6% (± 1.5%) for control arms (P < .0001). This reduction was driven by a significant drop in bone marrow-involved relapses (3.1% ± 0.8% vs 9.4% ± 1.3%), though isolated central nervous system (CNS) relapses remained unchanged.

The addition of blinatumomab largely mitigated the adverse effects of several traditional prognostic markers used in COG trials. In the control arms, Hispanic ethnicity was associated with a 2-fold increase in risk (HR 2.1), but in the blinatumomab arms, this risk was reduced (HR 1.3). In addition, end-of-induction MRD ≥ 0.01% was associated with a 4-year DFS of 82.3% (± 2.7%) in the control groups, while patients on blinatumomab MRD ≥ 0.01% had a superior 4-year DFS of 92.8% (± 1.9%). Patients with detectable levels of MRD who received blinatumomab even had a superior 4-year DFS to patients in the control group with favorable MRD levels (< 0.01%; DFS 89.7% ± 1.7%).

“While some adverse prognosticators retain significance in the context of blinatumomab-containing backbones, the addition of blinatumomab is of benefit for all examined subgroups, with most prognosticators losing significance,” the researchers concluded. “These results confirm this new standard therapy and have important implications for which subgroups could be considered for a reduction in traditional chemo in the future.”

Homecare Barriers Challenge Widespread Adoption

Despite the therapeutic success, the delivery required for blinatumomab is complex: a 28-day continuous intravenous infusion. This delivery, plus complex insurance reimbursement, has introduced significant real-world challenges, according to a survey of US COG institutions.²

A total of 149 COG institutions completed the 28-question survey. Close to all (90%) of institutes reported that blinatumomab was the standard of care for SR-average, SR-high, and high-risk B-ALL. Rates of blinatumomab were lower for infants (56%) and Philadelphia chromosome–positive (Ph+) ALL (65%). Infants have their own delivery challenges associated with low weight, and Ph+ is not part of the FDA approval of blinatumomab, the researchers noted. Centers not utilizing blinatumomab for these populations were significantly more likely to be small-volume centers.

A majority (62%) of centers reported at least 1 major care delivery barrier in the outpatient setting, and 36% reported 3 or more major barriers. The most frequent major barriers were lack of homecare companies (50%), distance to the treating center (28%), and insurance coverage for homecare (26%). Centers that didn’t use blinatumomab for infants and Ph+ patients also reported these populations were more likely to lack homecare companies.

The lack of homecare companies was particularly pronounced in the West (71%) and Northeast (61%) census regions compared with regions in the Midwest (44%) and South (43%) census regions.

Centers not utilizing blinatumomab for these challenging populations were significantly more likely to be small-volume centers and, for Ph+ ALL, were more likely to report a lack of homecare companies (67% vs 41%).

“The national variability in pediatric homecare is an important health system issue given potential implications for blinatumomab-related family burden in terms of inpatient admissions and emergency room visits, resource burden on hospitals, and our ability to implement large-scale pediatric outpatient care delivery beyond blinatumomab,” the researchers concluded.

References

1. Gupta S, Rau R, Kairalla J, et al. Blinatumomab mitigates the impact of traditional adverse prognosticators among children with standard risk b-acute lymphoblastic leukemia: updated results of the Children’s Oncology Group (COG) trial AALL1731. Presented at: ASH 2025; December 5-8, 2025; Orlando, Florida. Abstract 758.

2. Zheng D, Oranges K, Ramakrishnan S, et al. National landscape of real-world pediatric blinatumomab care delivery in the United States: a report from the Children's Oncology Group. Presented at: ASH 2025; December 5-8, 2025; Orlando, Florida. Abstract 1077.