GRAALL-2014 trial: Age-adapted chemotherapy and MRD-oriented transplant for Ph-negative ALL

The Group for Research on Adult Acute Lymphocytic Leukemia (GRAALL)-2014 trial (NCT02617004, NCT02619630) assessed the safety and efficacy of intensive age-adapted chemotherapy and measurable residual disease (MRD)-guided transplant in patients aged 18 to 59 years with Philadelphia chromosome-negative (Ph-negative) B-cell acute lymphoblastic leukemia (B-ALL; n = 489) or T-cell ALL (n = 254). The main endpoint was disease-free survival (DFS) at 4 years. Boissel et al. published findings from the trial, with a comparison to outcomes of the previous GRAALL-2005 trial, in Blood.

Key data: The GRAALL-2014 trial demonstrated overall 4-year disease-free survival (DFS) rates comparable with the GRAALL-2005 trial (57.1% vs 58.8%, respectively). GRALL-2014 demonstrated reduced non-relapse mortality (NRM) (p < 0.0001), particularly in patients ≥45 years. MRD-guided allogeneic hematopoietic stem cell transplantations (allo-HSCT) were reduced by 50%. GRAALL-2014 vs GRAALL-2005 showed a higher 4-year cumulative incidence of relapse (CIR) (37.6% vs 29.6%), while 4-year overall survival (OS) rates improved from 65.5% (GRAALL-2005) to 71.7% (GRAALL-2014) in younger patients and from 49.6% to 59.5% in older patients. 

Key learning: These findings highlight the benefit of tailored treatment approaches that balance efficacy with safety in younger adult patients with Ph-negative ALL. Research to investigate the addition of immunotherapy to further reduce treatment intensity and improve outcomes is needed.