Intensified chemotherapy regimens have improved outcomes in adults with Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (B-ALL), yet relapse remains a major cause of treatment failure and death. Blinatumomab, a CD19×CD3 bispecific T-cell engager, has demonstrated marked activity in relapsed, measurable residual disease (MRD)-positive B-ALL, and in frontline consolidation for MRD-negative patients. The phase 2 GRAALL-2014/B-QUEST sub-study (NCT02617004) evaluated the integration of blinatumomab into consolidation and maintenance therapy for adults with high-risk (HR) B-ALL treated within the GRAALL-2014/B trial. Between 2015 and 2020, 489 adults aged 18-59 years with newly diagnosed Ph-negative B-ALL were enrolled, among them 259 were classified as HR (presence of KMT2A-r, IKZF1 deletion, or end-of-induction MRD≥10-4). Ninety-four HR patients enrolled in QUEST (2018-2020) received up to five 28-day cycles of blinatumomab integrated into consolidation and maintenance. Ninety HR patients treated before QUEST activation without blinatumomab served as controls in a post hoc analysis. Baseline characteristics were comparable. Blinatumomab consolidation significantly improved MRD clearance, reduced relapse, and prolonged survival. At 5 years, cumulative incidence of relapse, disease-free survival (DFS), and overall survival were 23%, 68%, and 79% versus 49% (p=0.001), 42% (p=0.001), and 60% (p=0.03) in controls. Outcome benefit generally favored blinatumomab across subgroups, although not reaching significance in KMT2A-rearranged cases. Very high-risk patients eligible for alloHSCT derived overall benefit. However, no clear additional DFS advantage was observed among those ultimately transplanted. These findings support frontline integration of blinatumomab and warrant prospective evaluation of transplantation strategies in this setting.
Boissel et al. (Fri,) studied this question.