# A Modified-Delphi Consensus on the Management of Patients with FLT3-Mutated AML

## TL;DR

Experts in Italy created clear guidelines for treating blood cancer patients with FLT3 gene mutations using new drugs and transplants.

## Contribution

The paper provides evidence-based clinical recommendations for FLT3-mutated AML management through a modified Delphi consensus.

## Key findings

- FLT3 inhibitors combined with chemotherapy improve outcomes for fit patients with FLT3-mutated AML.
- MRD monitoring is recommended to guide stem cell transplant decisions and assess relapse risk.
- Gilteritinib is recommended as standard treatment for relapsed FLT3-mutated AML patients.

## Abstract

Acute myeloid leukemia (AML) is a fast-growing blood cancer. Many patients have alterations in a gene called FLT3, which were once linked to poor outcomes. New targeted medicines called FLT3 inhibitors have greatly improved treatment, but their use requires clear guidance. A group of Italian experts reviewed the available evidence and agreed on practical recommendations for treating patients with AML with FLT3 alterations. They recommend that all patients are tested for FLT3 alterations when they acknowledge to be sick. Patients who can receive intensive therapy should receive standard chemotherapy combined with an FLT3 inhibitor and be assessed for a potentially curative stem cell transplant. For patients who cannot receive intensive treatment, current options are often not effective enough, and better therapies are urgently needed. Monitoring small amounts of remaining leukemia after treatment is important to estimate relapse risk and guide transplant decisions. If the disease returns, FLT3 testing should be repeated, and treatment with the FLT3 inhibitor gilteritinib is recommended. Overall, FLT3 inhibitors have improved the outlook for patients with FLT3-mutated AML. This consensus provides clear, evidence-based advice to help doctors deliver more consistent and effective care.

Background/Objectives: The emergence of FLT3 inhibitors (FLT3i) has radically transformed the prognostic and therapeutic landscape for FLT3-mutated Acute Myeloid Leukemia, stimulating the need for comprehensive and structured clinical guidance. Methods: We aimed to develop evidence-based recommendations spanning the entire disease continuum of FLT3-mutated AML from leading Italian experts through a modified Delphi consensus process. Results: The panel achieved a high degree of agreement on specific interventions covering diagnostic testing, upfront FLT3i integration, role of allogeneic hematopoietic cell transplantation (allo-HSCT), Minimal Residual Disease (MRD) monitoring, and relapsed/refractory (R/R) strategies. Key recommendations mandate that analysis for both FLT3-ITD and FLT3-TKD mutations is required at diagnosis, with capillary electrophoresis or NGS as preferred methods. All fit patients with FLT3m-AML must receive intensive chemotherapy plus a FLT3i (midostaurin or quizartinib) and be evaluated for allo-HSCT. For unfit patients, the current standard of HMA + venetoclax is considered suboptimal, making the search for alternative strategies imperative. MRD monitoring using available molecular or flow cytometry markers is recommended to assess relapse risk and to optimize the allo-HSCT strategy. In the R/R setting, retesting the FLT3 status is mandatory, and gilteritinib is the standard treatment, serving as a bridge-to-transplant and for post-HSCT maintenance. Conclusions: The integration of FLT3i has shifted FLT3m-AML into a more favorable intermediate prognostic category, enhancing the role of curative strategies like allo-HSCT. This consensus paper provides a structured evidence-based comprehensive guide, translating complex data into clear actionable clinical recommendations that minimize practice variability and ultimately optimize management for this high-risk population.