Data from Integrated Analysis of Genomics, Molecular Responses, and Outcomes of CBF-AML with FLAG-Based Therapy on a Phase II Trial

作者：Jayastu Senapati, Hagop M. Kantarjian, Edward Ayoub, Andres Quesada, Sanam Loghavi, Koji Sasaki, Tapan M. Kadia, Naval Daver, Courtney D. DiNardo, Akhil Jain, Mikaela McCabe, Fadi Haddad, Mark Brandt, Guilin Tang, Yesid Alvarado, Kayla Farish, Hussein A. Abbas, Guillermo Garcia‐Manero, Farhad Ravandi, Michael Andreeff, Gautam Borthakur · 年份：2026 · DOI：10.1158/2643-3230.c.8568783 · 研究领域：Acute Myeloid Leukemia Research、Acute Lymphoblastic Leukemia research、Myeloproliferative Neoplasms: Diagnosis and Treatment

<div>AbstractFludarabine, cytarabine, and G-CSF–based therapy (FLAG) yields approximately 60% 5-year overall survival (OS) in core-binding factor (CBF) acute myeloid leukemia (AML), with potential added benefit with gemtuzumab ozogamicin (GO). Although measurable residual disease (MRD) status via optimal quantitative polymerase chain reaction (qPCR) response (OPR; qPCR <0.1% at the end of induction and <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 first-line patients with CBF-AML (median age 52 years; range, 19–80) treated on a phase II 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, respectively, 77% and 80% with FLAG-GO. On multivariate analysis, baseline mutations did not affect OPR or survival, whereas FLAG-GO favored both. In CBF-AML, FLAG-based therapy possibly attenuates the prognostic impact of concurrent baseline genomics.Significance:In CBF-AML treated with conventional intensive chemotherapy, usually 7 + 3, baseline mutations in KIT, chromatin modulators, cohesin complex, etc., garner suboptimal MRD clearance and surviv...