Blinatumomab consolidation for high-risk Ph− B-cell acute lymphoblastic leukemia: the GRAALL-2014/B-QUEST study

ABSTRACT: Intensified chemotherapy regimens have improved outcomes in adults with Philadelphia chromosome-negative (Ph-) B-cell acute lymphoblastic leukemia (B-ALL), yet relapse remains a major cause of treatment failure and death. Blinatumomab is a T-cell engager that demonstrated marked activity in relapsed and measurable residual disease-positive (MRD+) B-ALL, as well as in frontline consolidation for MRD- patients. The phase 2 GRAALL-2014/B-QUEST substudy evaluated the integration of blinatumomab into consolidation and maintenance therapy for adults with high-risk (HR) B-ALL. Between 2015 and 2020, 489 adults aged 18 to 59 years with newly diagnosed Ph- B-ALL were enrolled, and among these 259 were classified as HR (presence of KMT2A-r, IKZF1 deletion, or end-of-induction MRD ≥ 10-4). A total of 94 patients with HR were enrolled in the QUEST study (2018-2020) and received up to 5, 28-day cycles of blinatumomab during consolidation and maintenance. In addition, 90 patients with HR who were treated before QUEST activation without blinatumomab served as controls in a post hoc analysis. Baseline characteristics were comparable between groups. 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% in the blinatumomab group compared with 49% (P = .001), 42% (P = .001), and 60% (P = .03) in controls. Patients eligible for allogeneic hematopoietic stem cell transplantation (alloHSCT) derived overall benefit. However, no clear additional DFS advantage was observed among those who ultimately underwent transplantation. These findings support the frontline integration of blinatumomab and warrant prospective evaluation of transplantation strategies in this setting. This trial was registered at www.clinicaltrials.gov as #NCT03709719.