ECOG-ACRIN E1910 study: Genomic subtypes and blinatumomab response in adult B-ALL

Results from an analysis of genomic and clinical data from 569 adults with newly diagnosed (ND) B-cell acute lymphoblastic leukemia (B-ALL) who were registered for initial screening in the phase III ECOG-ACRIN E1910 (NCT02003222) study of blinatumomab were published in Blood by Zong and Roberts et al. 

Key data: A total of 23 molecular subtypes were identified; high-risk subtypes were common, including BCR::ABL1 (20%), BCR::ABL1-like (18%), low hypodiploid (14%) and KMT2A-reaarangment (KMT2A-R; 12%). Among patients with BCR::ABL1-negative B-ALL and available outcomes data (n = 331), those who were non-MRD-negative more frequently had BCR::ABL1-like (34.3% vs 13.9%) and KMT2A-R (19.0% vs 9.3%) subtypes but less frequently had PAX5-altered (5.1% vs 17.5%), TCF3::PBX1 (0% vs 4.6%), and ZNF384-R (0.7% vs 5.7%) subtypes than the MRD-negative group. Among MRD-negative patients, blinatumomab + chemotherapy showed a trend towards improved 3-year relapse-free survival (RFS) and overall survival (OS) vs chemotherapy alone in hyperdiploid, PAX5-alteration, BCR::ABL1-like JAK-STAT, and KMT2A-R B-ALL but not in low hypodiploid B-ALL.

Key learning: The results of this analysis suggest potential differences in the efficacy of blinatumomab + chemotherapy across genomic subtypes in adults with BCR::ABL1-negative B-ALL; validation in larger, prospective studies is needed.