Thank you for visiting

By clicking "Continue," you will leave this site.
CONTINUE

This website is funded and developed by Astellas Pharma US, Inc.

FLT3 mutations.

The Impact of FLT3 Mutations in AML

In patients with AML,

FLT3 is the most common mutation at diagnosis and is associated with lower* patient survival2,3

While there are many mutations in AML, it has been shown that, of patients newly diagnosed with AML and tested for FLT3 mutations, up to 1 in 3 patients may have a FLT3 mutation.2


*FLT3-ITD.
AFTER INDUCTION THERAPY5

The 5-year survival rate is as low as 15% in patients with a FLT3-ITD mutation5

Chart of 5‐year survival rates in AML patients with a FLT3‐ITD mutation. Chart of 5‐year survival rates in AML patients with a FLT3‐ITD mutation.

Data from DNA samples of 1425 young adult patients with AML (1307 with de novo AML) treated with conventional chemotherapy who entered into 2 clinical trials between 1988 and 2002. Overall survival stratified according to total FLT3-ITD level. Shown here: The distribution of FLT3/ITD cases according to total mutant level suggested 3 different groups: those with less than 25% mutant (low), 25% to 50% mutant (intermediate), and greater than 50% mutant (high).


ITD=internal tandem duplication.

At relapse3

Overall survival rate is more than 1.5x lower in patients with FLT3-ITD mutation-positive relapsed/refractory AML3

2-YEAR OVERALL SURVIVAL RATE3

40%*

survival with
no FLT3-ITD mutation (n=96)

23%*

survival with
FLT3-ITD (n=37)

*±5 for no mutation and ±7 for FLT3-ITD.

Data from a retrospective, multicenter study including 138 adult patients with refractory (n=57) or relapsed (n=81) AML treated with a combination of gemtuzumab ozogamicin and intensive salvage chemotherapy (96 patients had no FLT3-ITD mutation, 37 had FLT3-ITD mutation, and 5 had an unknown mutation status).

The prevalence of FLT3-ITD mutations can increase with each relapse6*

Mutation status changes throughout treatment6*

22%

of patients had a change in mutational status at relapse (n=11/50)6

  • 10% GAINED a FLT3-ITD mutation (5/50)
  • 8% LOST a FLT3-ITD mutation (4/50)
  • 4% CHANGED mutational status from FLT3-TKD  to FLT3-ITD  (2/50)

Incidence of a FLT3 mutation can increase with each relapse,* and may lead to lower overall survival rates3,5,6

DIAGNOSIS

22%

of patients had a
FLT3-ITD  mutation

AT DIAGNOSIS6

(n=11/50)

DIAGNOSIS

22%

of patients had a FLT3-ITD  mutation AT DIAGNOSIS6  (n=11/50)
1ST RELAPSE

32%

of patients had a
FLT3-ITD  mutation

AT 1ST RELAPSE6

(n=16/50, P=0.37)

1ST RELAPSE

32%

of patients had a FLT3-ITD  mutation AT 1ST RELAPSE6  (n=16/50, P=0.37)
2ND RELAPSE

43%

of patients had a
FLT3-ITD  mutation

AT 2ND RELAPSE6

(n=6/14, P=0.17)

2ND RELAPSE

43%

of patients had a FLT3-ITD  mutation AT 2ND RELAPSE6  (n=6/14, P=0.17)

*A retrospective analysis of 50 adult patients with FLT3 mutations at diagnosis and relapse with chemoresistant AML to correlate mutation status with multiple variables.6


TKD=tyrosine kinase domain.

A FLT3 mutation can develop through clonal evolution7

Clonal evolution during therapy can lead to a change in mutational status7

Chart of clonal evolution during therapy, which can lead to a change in mutational status.
GENETICALLY DIFFERENT AML CLONES
Clone with early founder mutation
Initial driver mutation clone with disease-defining mutation
Late driver mutation additional subclones
  • AML cells often gain or lose mutations, including FLT3 mutations, and these cells can proliferate8
  • Some clones may become dominant, while others may emerge, leading to a change in mutation status 8

FLT3 mutation status can change, thus it is important to test patients at relapse or progression.1,6

Learn about testing for mutations
Think FLT3 brochure.

Learn more about FLT3 mutations in AML and the associated risks

Download the brochure
Download the brochure
A tornado moving toward a cityscape. A tornado moving toward a cityscape.