The use of blinatumomab during consolidation for high-risk (HR) Philadelphia chromosome (Ph)-negative B-Cell precursor (BCP) acute lymphoblastic leukemia (ALL), was associated with reduced relapse rates, according to findings from a nested 2-cohort comparison sub-study within the GRAALL-2014/B trial. 

At the 2022 ASH Annual Meeting and Exposition in New Orleans, LA, Nicolas Boissel, MD, PhD, St-Louis Hospital, Paris, France, and colleagues presented the data from the GRAALL-2014/B study, which included a nested phase2 QUEST sub-study and a control cohort.

Among the 489 total participants in the GRAALL-2014/B study, 266 presented with high-risk features (defined as carrying KMT2A-rearrangement, IKZF1 intragenic deletion, and/or IG/TR post-induction molecular residual disease (MRD) ≥10-4) and were offered enrollment into the nested phase 2 QUEST sub-study. Those patients that enrolled (evaluable, n = 94) received blinatumomab during consolidation and maintenance, or as a bridge to allogeneic hematopoietic stem cell transplantation (HSCT). The outcomes measured were disease-free survival (DFS), measurable residual disease evolution (MRD), relapse, and overall survival (OS). The control cohort (n = 104) used for comparison included similar patients treated in the GRAALL-2014/B trial, without frontline blinatumomab.

Among all patients with MRD2 ≥ 10-4, the rate of undetectable MRD at MRD3 was 56% (23/41) after treatment with blinatumomab, compared with 14% (4/29) after chemotherapy alone (P < .001). There was no statistically significant difference in rate of HSCT in the first complete response between the cohorts. The blinatumomab cohort had a lower cumulative incidence of relapse (sub-distribution hazard ratio [SHR] 0.48; 95% confidence interval [CI], 0.28 to 0.83; P = .009) and a prolonged DFS (HR 0.59; 95% CI, 0.37 to 0.96; P = .03), compared with the control cohort. There was no difference in OS between the 2 cohorts (HR 0.67; 95% CI, 0.36 to 1.25; P =0.21). Dr  Boissal et al stated, “These differences were also observed after censoring patients at the time of allo-HSCT, or when excluding from the control group patients not enrolled in the QUEST study during the accrual period.”

Dr Boissal et al concluded this study “suggests that blinatumomab in consolidation benefits [high-risk] Ph-negative BCP-ALL patients by markedly reducing the risk of relapse.” There are currently phase 3 trials both planned and ongoing to confirm these data. 

Source: 
Boissel N, Huguet Fm Leguay T, et al. Blinatumomab during Consolidation in High-Risk Philadelphia Chromosome (Ph)-Negative B-Cell Precursor (BCP) Acute Lymphoblastic Leukemia (ALL) Adult Patients: A Two-Cohort Comparison within the Graall-2014/B Study. Presented at ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA. Abstract 211