CLEVO

• Research type

  Research Study

• Full title

  A non-interventional cohort study of the CLonal EVOlution of FLT3 mutations during disease progression in patients with acute myeloid leukemia.

• IRAS ID

  278955

• Contact name

  Paresh Vyas

• Contact email

  paresh.vyas@imm.ox.ac.uk

• Sponsor organisation

  Astellas Pharma Europe Ltd

• Duration of Study in the UK

  4 years, 7 months, 12 days

• Research summary

  Research Summary
  The aim of this study is to characterize the FLT3 gene mutations identified at
  diagnosis, the clonal evolution of FLT3 mutations (gain or loss) during the course of the disease, the effect of common AML treatments on the clonal evolution of FLT3 mutations, and to describe the profile of AML patients with clonal evolution.

  Summary of Results
  This was a non-interventional cohort study examining the clonal evolution of FLT3 mutations in patients with acute myeloid leukemia (AML).
  The study enrolled 650 AML patients across 8 countries and followed them for up to 3 years.
  Key Findings:

  Clonal Evolution of FLT3 Mutations:

  At first relapse, 77.8% of initially FLT3-positive patients retained their status, while 85.2% of FLT3-negative patients remained negative.
  Over 10% of patients showed FLT3 clonal evolution (gain or loss of mutations) at first relapse/refractory occurrence.
  Survival Outcomes:

  FLT3-positive patients showed better overall survival at baseline compared to FLT3-negative patients.
  No significant differences in disease-free or event-free survival between FLT3-positive and negative patients.
  Treatment Response:

  60.9% of patients achieved composite complete remission (CRc) at baseline.
  Higher CRc rates with high-intensity chemotherapy + FLT3 inhibitors (80.6%) vs chemotherapy alone (73.1%) or hypomethylating agents + venetoclax (48.7%).
  Genetic Landscape:

  65.1% of patients had other AML-associated genetic mutations at baseline, most commonly NPM1 and IDH1/2.
  49.7% had cytogenetic changes at baseline, with complex karyotype being common.
  Conclusions:

  Significant clonal evolution of FLT3 mutations occurs throughout AML progression.
  Regular FLT3 testing is needed to optimize treatment, especially at relapse/refractory stages.
  FLT3 mutation status may have complex relationships with treatment outcomes that warrant further study.
  Findings have implications for personalized treatment approaches in AML.
  Limitations included decreasing sample sizes at later disease stages and potential biases in genetic testing methodologies across sites.

• REC name

  North West - Greater Manchester Central Research Ethics Committee

• REC reference

  20/NW/0356

• Date of REC Opinion

  17 Aug 2020

• REC opinion

  Favourable Opinion