In the phase III ECOG-ACRIN E1910 trial reported in The New England Journal of Medicine, Mark R. Litzow, MD, and colleagues found that the addition of blinatumomab to consolidation chemotherapy improved overall survival among adult patients with BCR-ABL fusion–negative B-cell precursor acute lymphoblastic leukemia (BCP-ALL) who were measurable residual disease (MRD)-negative after induction and intensification chemotherapy.
Mark R. Litzow, MD
Study Details
The trial included 224 patients aged 30 to 70 years from sites in Canada, Israel, and the United States with MRD-negative remission (< 0.01% leukemic cells in bone marrow on flow cytometry) after induction and intensification chemotherapy. They were randomly assigned to receive two cycles of blinatumomab at 28 μg per day for 4 weeks with a 2-week interval between cycles, followed by four cycles of chemotherapy and two additional cycles of blinatumomab (n = 112) or four cycles of consolidation chemotherapy only (n = 112).
The primary endpoint of the study was overall survival.
Overall Survival
In September 2022, the ECOG-ACRIN data and safety monitoring committee reviewed the results of the third efficacy interim analysis at a median follow-up of 43 months and recommended release of the results.
At a median follow-up of 43 months, 3-year overall survival was 85% in the blinatumomab group vs 68% in the chemotherapy group (hazard ratio [HR] = 0.41, 95% confidence interval [CI] = 0.23–0.73, P = .002); the result crossed the stopping boundary for efficacy (P = .007).
Relapse-free survival at 3 years was 80% in the blinatumomab group vs 64% in the chemotherapy group (HR = 0.53, 95% CI = 0.32–0.87).
Adverse Events
For the blinatumomab group vs the chemotherapy group, during consolidation, grade 3 treatment-related nonhematologic adverse events occurred in 43% vs 36% of patients, grade 4 events in 14% vs 15%, and grade 5 events in 2% vs 1% (overall P = .87). Grade 3 or 4 treatment-related hematologic toxicities included neutropenia (58% vs 87%) and thrombocytopenia (49% vs 69%).
Treatment-related grade ≥ 3 neurologic or psychiatric adverse events occurred in 23% of the blinatumomab group vs 5% of the chemotherapy group (P < .001).
The investigators concluded, “The addition of blinatumomab to consolidation chemotherapy in adult patients in MRD-negative remission from BCP-ALL significantly improved overall survival.”
Dr. Litzow, of the Division of Hematology, Mayo Clinic, Rochester, is the corresponding author for The New England Journal of Medicine article.
Disclosure: The study was funded by the National Institutes of Health and others. For full disclosures of the study authors, visit nejm.org.
