Exploring the Heterogeneity of Response to Blinatumomab in High-Risk Philadelphia-Negative B-Cell Precursor Acute Lymphoblastic Leukemia: An Analysis from the QUEST Sub-Study of the Graall-2014/B Trial

Introduction. Adults with Philadelphia (Ph)-negative B-cell precursor acute lymphoblastic leukemia (BCP-ALL) benefit from blinatumomab (BLIN) in first-line consolidation. However, the magnitude of this benefit according to baseline patient and disease characteristics remains largely unexplored. In the GRAALL-2014/B QUEST sub-study, patients with high-risk (HR) features (i.e. post-induction MRD1 ≥10 -4, IKZF1 intragenic deletion, or KMT2A rearrangement) received BLIN during consolidation. Patients eligible to receive an allogeneic hematopoietic stem cell transplant (allo-HSCT) in first complete remission (CR) (i.e. those with late CR, or post-induction MRD1 ≥10 -3, or post-consolidation MRD2 ≥10 -4) received only one BLIN cycle before transplant. A control cohort was established from patients enrolled in the same protocol who exhibited the same HR criteria but did not receive BLIN in first CR. The objective of this analysis was to identify patient- and disease-related factors associated with response to BLIN, and to understand how BLIN influences the outcome after allo-HSCT.