Treatment decisions in AML: Personalizing care with FLT3 inhibitor therapy

During a meeting of the AML Hub Steering Committee, held on February 19, 2026, Jorge Sierra chaired a discussion on the topic, Treatment decisions in AML: Personalizing care with FLT3 inhibitor therapy. The discussion featured contributions from Charles Craddock, Jorge Cortes, Hee-Je Kim, Jeffrey Lancet, Yasushi Miyazaki, Uwe Platzbecker, Roland Walter, and Agnieszka Wierzbowska.

Sierra first provided an overview of the role of FLT3 mutations in acute myeloid leukemia (AML) pathogenesis, and highlighted key considerations when making treatment decisions for patients with FLT3-mutated (FLT3m) AML, such as the European Leukemia Network (ELN) 2022 and 2024 risk classifications (Figure 1). He summarized key combination strategies for the treatment of AML (Figure 2), and shared updates from the 67th American Society of Hematology Annual Meeting and Exposition and the European Hematology Association 2025 Congress on triplet regimens including the FLT3 inhibitors gilteritinib and quizartinib. The discussion centered around preferred approaches to personalizing care in two patient cases.

Key points

First-line treatment strategy in a 60-year-old fit patient with FLT3-ITD AML, with concomitant NPM1 and DNMT3A mutations

• The preferred treatment approach would be 7+3 plus a FLT3 inhibitor, such as quizartinib or gilteritinib; promising safety and efficacy data have been reported with quizartinib triplet therapy in this population, in the QuANTUM-First trial (NCT02668653).⁵
• If measurable residual disease (MRD)-positive complete remission (CR) or CR with incomplete hematologic recovery (CRi) following induction and consolidation was achieved, proceeding directly to allogeneic hematopoietic stem cell transplantation (allo-HSCT) with FLT3 inhibitor maintenance would be preferred, given uncertainty around whether attempts to convert MRD positivity to negativity prior to transplantation would translate into meaningful survival benefits.
  • Optimal selection of post-transplantation maintenance therapy remains an unmet clinical need. Gilteritinib is well supported by evidence; however, studies investigating quizartinib for post-transplantation maintenance in FLT3-ITD AML are underway.
• In MRD-negative CR/CRi after induction and consolidation, an MRD-guided approach, with transplantation delayed until MRD positivity recurred, or consideration of allo-HSCT if the patient was fit and had a suitable donor, was discussed.

First-line treatment strategy in a 70-year-old unfit patient with FLT3-ITD AML, with concomitant SF3B1 and IDH1 mutations

• The preferred approach would be a triplet combination of venetoclax (Ven) + azacitidine (Aza) and a FLT3 inhibitor.
  • Greater long-term benefit has been demonstrated with such triplet regimens than with Ven + Aza doublet regimens in patients with FLT3-ITD AML.⁹
  • Important considerations for managing FLT3m AML with triplet regimens include close monitoring for myelosuppression and toxicity.
• If MRD-positive CR was achieved, initial therapy should be continued, due to the variability in fitness and treatment tolerance, and potential for rapid clinical deterioration, in older patient populations.

This educational activity is independently supported by Daiichi Sankyo. All content was developed by the faculty in collaboration with SES. Funders were allowed no influence.