Multi-center acute myeloid leukemia study

Update provided by Prof Maria Teresa Voso in December 2023.

Full project title

Evaluation of the prognostic impact of subclonal FLT3-ITD mutations in acute myeloid leukemia (AML): a retrospective multi-center study on behalf of the EHA AML-SWG.

Project team

  • The Principal Investigator is Prof Maria Teresa Voso.
  • The Co-Principal Investigator is Dr Carmelo Gurnari.

Interim results

Thanks to the support of the EHA SWG ‘seeding call’ grant received in 2022, we were able to gather an international consortium of eight academic centers who agreed to participate in this research effort. These centers are located across Europe, in Italy, Spain, Poland, Germany, and the UK.

We enrolled patients:

  • In clinical trials
  • Diagnosed according to the standard clinical practice between 2017 and 2022

In total, we collected clinical and molecular information on 269 patients with AML and a subclonal FLT3-ITD mutation (allelic ratio of less than 0.05), from a population of over 7,000 newly diagnosed AML patients.

At the moment, we are still gathering information on the total number of AML patients diagnosed in the respective centers in the time frame (which is the ‘denominator’). However, we successfully completed the data collection and harmonization phases, and are now in the process of data analysis.

Challenges

The biggest challenge has been the collection by the different centers of detailed clinical information on the patients, since only few groups had been prospectively collecting data on the FLT3-ITD subclones at diagnosis.

A second issue has been that, for some patients, data on FLT3 mutations status at relapse was not available, and some re-testing had to be performed. However, given the high interest of the project, almost all centers who initially agreed to participate were able to fill the required information by November 2023.

Future plans

Our aim is to submit an abstract describing the major findings of this project at the next EHA Congress, to be held in Madrid in June 2024, and possibly at the 2024 ASH meeting.

Shedding light on FLT3-ITD mutations

In parallel, we will finalize a manuscript that will shed light on the role of subclonal FLT3-ITD mutations.

Up to 2022, the threshold to define FLT3-ITD positivity was conventionally set at an allelic ratio of 0.05 by capillary electrophoresis. However, recent data and our clinical practice suggest that FLT3-ITD mutations maintain their negative prognostic potential and predict for an increased risk of relapse even when present at a subclonal state. These cases may be indeed under-diagnosed and present as overt FLT3-ITD-mutated AML at relapse.

Drawing upon the collaborative power of European AML centers that we've built with this project, our aim is to consolidate the thresholds for the definition of FLT3-ITD positivity at AML diagnosis. This will open up the possibility of expanding the use of FLT3-inhibitory drugs in patients harboring FLT3-ITD subclones.

Budget and cost estimations

Activity Cost
 Data collection and harmonization (20 hrs/month, 8 months)  €7500
 Statistician support  €5000
 Abstract submission and presentation at EHA Congress  €2000
 Abstract submission and presentation at ASH meeting  €2500
 Publication costs  €3000