Abstract
Fludarabine, cytarabine, and G-CSF-based therapy (FLAG) yields approximately 60% 5-year overall survival (OS) in core-binding factor (CBF) AML, with potential added benefit with gemtuzumab ozogamicin (GO). Although measurable residual disease status via optimal quantitative PCR response (OPR; qPCR <0.1% at end-of-induction, <0.01% during/after consolidation) of fusion-transcripts predicts survival, the impact of baseline myeloid mutations on OPR and survival, with FLAG remains uncertain. We interrogated these factors in 219 frontline patients with CBF-AML (median age 52 years; range 19-80) treated on a phase 2 trial (NCT00801489); 51% received FLAG-GO and 49% FLAG-idarubicin. Baseline mutations included 49% kinase-pathways (non-MAP kinase), 44% MAP-kinase, 11% DNMT3A-ASXL1-TET2 and 7% transcription-factors. Five-year relapse-free survival and OS were 67% and 74% overall; 77% and 80% with FLAG-GO. On multivariate analysis, baseline mutations did not affect OPR or survival, while FLAG-GO favored both. In CBF-AML, FLAG-based therapy possibly attenuates the prognostic impact of concurrent baseline genomics.