An all-oral triplet regimen (decitabine/cedazuridine, venetoclax, and gilteritinib) for newly diagnosed and relapsed/refractory FLT3-mutated AML and high-risk MDS
Combination of FLT3 inhibitors with azacitidine and venetoclax has promising activity in FLT3 -mutated acute myeloid leukemia (AML). In this phase I/II study, we evaluated the safety and efficacy of an all-oral regimen of decitabine/cedazuridine, venetoclax, and gilteritinib in adults with FLT3 -mutated AML and other myeloid malignancies. A total of 46 patients were enrolled (19 with newly diagnosed [ND] AML and 27 with relapsed/refractory [R/R] disease). The median age was 72 years in ND AML and 67 years in R/R cohort; 38 patients (83%) had FLT3 -ITD mutations. The composite complete remission (CRc) rate was 74% in ND-AML and 42% in R/R-AML, with CR rates of 58% and 21%, respectively. Two nonresponders in the ND group had prior treatment for antecedent myeloid malignancies. The 18-month relapse-free survival and overall survival were 67% and 54% in the ND cohort, respectively. During induction, the median time to ANC ( > 0.5 × 10⁹/L) and platelet ( > 50 ×10⁹/L) recovery was 37 and 27 days, respectively, in ND AML. During consolidation, median treatment durations were 3 days for DEC-C, 7 days for venetoclax, and 28 days for gilteritinib. This all-oral triplet regimen shows promising activity in ND FLT3 -mutated AML; myelosuppression remains a key toxicity requiring dose adjustment.
Authors
- Farhad Ravandi (ORCID: https://orcid.org/0000-0002-7621-377X)
- Courtney Denton Dinardo (ORCID: https://orcid.org/0000-0001-9003-0390)
- Wei‐Ying Jen (ORCID: https://orcid.org/0000-0002-9339-3362)
- Steven Mitchell Kornblau (ORCID: https://orcid.org/0000-0002-5990-9548)
- Tapan Mahendra Kadia (ORCID: https://orcid.org/0000-0002-9892-9832)
- Guillermo Montalban‐Bravo (ORCID: https://orcid.org/0000-0002-4533-5176)
- Kelly Sharon Chien (ORCID: https://orcid.org/0000-0001-6024-1613)
- Álex Bataller (ORCID: https://orcid.org/0000-0002-6085-2745)
- Naval Guastad Daver (ORCID: https://orcid.org/0000-0001-7103-373X)
- Elias Joseph Jabbour (ORCID: https://orcid.org/0000-0003-4465-6119)
- Musa E. Yilmaz (ORCID: https://orcid.org/0000-0002-4498-4895)
- Gautam M. Borthakur (ORCID: https://orcid.org/0000-0001-7679-6453)
- Xuelin Huang (ORCID: https://orcid.org/0000-0003-1192-9336)
- Ghayas C. Issa (ORCID: https://orcid.org/0000-0002-4339-8683)
- Alexandre Bazinet (ORCID: https://orcid.org/0000-0001-5538-4943)
- Guillermo Garcia‐Manero (ORCID: https://orcid.org/0000-0002-3631-2482)
- Jayastu Senapati (ORCID: https://orcid.org/0000-0002-6831-2567)
- Hagop M. Kantarjian (ORCID: https://orcid.org/0000-0002-1908-3307)
- Nicholas James Short (ORCID: https://orcid.org/0000-0002-2983-2738)
- Roberta Santos Azevedo (ORCID: https://orcid.org/0009-0004-2997-6071)
- Wei Qiao
- Dono Tippett
Institutions
- The University of Texas MD Anderson Cancer Center (US)
Publication Details
- Journal
- Blood Cancer Journal
- Published
- 2026-10-13
- DOI
- https://doi.org/10.1038/s41408-026-01643-3
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Astex Pharmaceuticals
- University of Texas MD Anderson Cancer Center