GRAALL-2014/B-QUEST phase II trial: Blinatumomab in adult high-risk Ph-negative B-ALL

Results from the multicenter, open-label, phase II GRAALL-2014/B-QUEST trial (NCT03709719), evaluating blinatumomab during consolidation and maintenance in 94 adult patients with high-risk Philadelphia chromosome-negative (Ph−) B-cell acute lymphoblastic leukemia (B-ALL), were published in Blood by Boissel et al. A control cohort of 90 patients treated on the same protocol prior to QUEST activation received chemotherapy alone. The primary objective was to demonstrate that the 3-year disease-free survival (DFS) rate was improved from the historical reference of 50% to 65%. 

Key data: The 3-year DFS in patients receiving blinatumomab was 70% (95% confidence interval [CI], 60−78) vs 48% in the control cohort. At 5 years, cumulative incidence of relapses (CIR), DFS, and overall survival (OS) were 23%, 68%, and 79% in the blinatumomab group vs 49% (p = 0.001), 42% (p = 0.001), and 60% (p = 0.03) in the control group. Blinatumomab significantly improved measurable residual disease (MRD) clearance after consolidation 2 compared with chemotherapy alone (undetectable MRD, 72% vs 55%; p = 0.041). In eligible patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), prior exposure to blinatumomab was not associated with a significant DFS advantage (hazard ratio [HR], 0.76; 95% CI, 0.39–1.50). 

Key learning: Blinatumomab consolidation significantly reduced relapses and improved survival in adults with high-risk Ph− B-ALL, supporting its frontline integration. However, the additional benefit of allo-HSCT in this context warrants prospective evaluation.