Integrated analysis of genomics, molecular responses and outcomes of CBF-AML with FLAG based therapy on a phase 2 trial
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.
Authors
- Farhad Ravandi (ORCID: https://orcid.org/0000-0002-7621-377X)
- Courtney Denton Dinardo (ORCID: https://orcid.org/0000-0001-9003-0390)
- Tapan Mahendra Kadia (ORCID: https://orcid.org/0000-0002-9892-9832)
- Andres Quesada (ORCID: https://orcid.org/0000-0002-5304-7828)
- Naval Guastad Daver (ORCID: https://orcid.org/0000-0001-7103-373X)
- Edward Ayoub (ORCID: https://orcid.org/0000-0003-1321-0114)
- Gautam M. Borthakur (ORCID: https://orcid.org/0000-0001-7679-6453)
- Sanam Loghavi (ORCID: https://orcid.org/0000-0001-8980-3202)
- Mark Brandt
- Guillermo Garcia‐Manero (ORCID: https://orcid.org/0000-0002-3631-2482)
- Mikaela McCabe
- Yesid Alvarado (ORCID: https://orcid.org/0000-0002-1652-7937)
- Hussein A. Abbas (ORCID: https://orcid.org/0000-0003-2946-3562)
- Michael Andreeff (ORCID: https://orcid.org/0000-0002-1144-1958)
- Jayastu Senapati (ORCID: https://orcid.org/0000-0002-6831-2567)
- Akhil Jain (ORCID: https://orcid.org/0000-0001-7298-4246)
- Kayla Farish
- Koji Sasaki
- Hagop M. Kantarjian (ORCID: https://orcid.org/0000-0002-1908-3307)
- Guilin Tang (ORCID: https://orcid.org/0000-0002-9482-4806)
- Fadi G. Haddad (ORCID: https://orcid.org/0000-0002-9702-8485)
Institutions
- The University of Texas MD Anderson Cancer Center (US)
- University of Iowa Health Care (US)
Publication Details
- Journal
- Blood Cancer Discovery
- Published
- 2026-04-14
- DOI
- https://doi.org/10.1158/2643-3230.bcd-25-0477
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- University of Texas MD Anderson Cancer Center