Blinatumomab (Blincyto) has gained FDA approval for consolidation therapy in adult and pediatric patients (1 month and older) with CD19-positive, Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (B-ALL), irrespective of minimal residual disease (MRD) status. This approval, granted in June 2024, marks a significant expansion of blinatumomab's role in B-ALL management.
The approval was based on the phase 3 ECOG-ACRIN E1910 study (NCT02003222), which demonstrated a significant overall survival (OS) benefit with the addition of blinatumomab to multiphase consolidation chemotherapy. In this trial, patients receiving blinatumomab (n = 112) showed superior OS compared to those receiving chemotherapy alone (n = 112). The 3-year OS rates were 84.8% (95% CI, 76.3%-90.4%) versus 69.0% (95% CI, 58.7%-77.2%), respectively, while the 5-year OS rates were 82.4% (95% CI, 73.7%-88.4%) versus 62.5% (95% CI, 52.0%-71.3%). The hazard ratio for 5-year OS was 0.44 (95% CI, 0.25-0.76).
Impact on Treatment Paradigm
"The idea of incorporating blinatumomab as consolidation regardless of MRD status has become a standard of care," said Daniel DeAngelo, MD, PhD, professor of medicine at Harvard Medical School and chief of the Division of Leukemia at Dana-Farber Cancer Institute. He added that this standard now extends beyond just the adult population, regardless of the backbone chemotherapy used.
Adam DuVall, MD, MPH, assistant professor of medicine and pediatrics at the University of Chicago Medicine, highlighted the evolving role of blinatumomab in pediatric, adolescent and young adult (AYA), and adult ALL, reshaping frontline and consolidation strategies. However, DuVall noted that unanswered questions remain regarding optimal patient selection, treatment sequencing, and the necessity of allogeneic stem cell transplant (alloHCT), underscoring the need for further randomized data to guide its use in high-risk patient populations.
Key Considerations and Ongoing Research
While the E1910 study included patients aged 30 to 70, there were few patients aged 30 to 40 or over 55. DuVall questioned whether certain MRD-negative patients might not benefit from blinatumomab, particularly those with deeper MRD negativity as detected by next-generation sequencing (NGS).
Data from the 2024 ASH Annual Meeting further elucidated blinatumomab's role. A study assessing outcomes with blinatumomab and alloHCT in MRD-negative B-lineage ALL showed that patients who are MRD negative do not need an alloHCT transplant, and that need for alloHCT is not impacted by blinatumomab. The phase 3 Children’s Oncology Group study AALL1731 (NCT03914625) demonstrated that blinatumomab plus chemotherapy improves disease-free survival in newly diagnosed NCI standard-risk pediatric B-ALL.
An analysis of blinatumomab consolidation among older patients with newly diagnosed B-Lineage ALL from ECOG-ACRIN E1910 indicated that patients randomly assigned to the blinatumomab arm did not experience an OS or relapse-free survival benefit in this age group (defined as greater than 55 years). However, the study was limited by a small sample size.
Blinatumomab in Ph-Positive ALL
For Philadelphia chromosome-positive (Ph-positive) ALL, combinations of blinatumomab with tyrosine kinase inhibitors (TKIs) are being explored to reduce reliance on chemotherapy and transplant. Studies evaluating blinatumomab with ponatinib have shown impressive OS without transplant.
Future Directions
Ongoing research aims to optimize blinatumomab use, determine the appropriate number of cycles, and identify patient populations that benefit most. Clinical trials are needed to address the lack of data for high-risk pediatric and AYA patients. According to DuVall, this data is crucial for providing patients with clear treatment recommendations and reducing psychosocial distress associated with uncertainty.
