What is FLT3 mutation?

Acute myeloid leukemia (AML) is divided into subtypes based on how the cancer cells look, and what gene changes they have. Some types of AML are more aggressive than others and need different treatment.

FLT3 is a gene change, or mutation, in leukemia cells. Between 20 and 30 percent of people with AML have this mutation.

The FLT3 gene codes for a protein called FLT3 that helps white blood cells grow. A mutation in this gene encourages the growth of too many abnormal leukemia cells.

People with the FLT3 mutation have a very aggressive form of leukemia that’s more likely to come back after it’s treated.

In the past, AML treatments weren’t very effective against cancers with the FLT3 mutation. But new drugs that specifically target this mutation are improving the outlook for people with this AML subtype.

The FLT3 gene helps regulate cell survival and reproduction. The gene mutation causes immature blood cells to multiply uncontrollably.

As a result, people with the FLT3 mutation have a more severe form of AML. Their disease is more likely to come back, or relapse, after treatment. They also have a lower survival rate than people without the mutation.

Symptoms of AML include:

  • easy bruising or bleeding
  • nosebleeds
  • bleeding gums
  • tiredness
  • weakness
  • fever
  • unexplained weight loss
  • headaches
  • pale skin

The College of American Pathologists and the American Society of Hematology recommend that everyone who is diagnosed with AML get tested for the FLT3 gene mutation.

Your doctor will test you in one of two ways:

  • Blood test: Blood is taken from a vein in your arm and sent to a lab.
  • Bone marrow aspiration: A needle is inserted into your bone. The needle removes a small amount of liquid bone marrow.

The blood or bone marrow sample is then tested to see if you have the FLT3 mutation in your leukemia cells. This test will show whether you’re a good candidate for drugs that specifically target this type of AML.

Until recently, people with the FLT3 mutation were mainly treated with chemotherapy, which wasn’t very effective at improving survival rates. A new group of drugs called FLT3 inhibitors is improving the outlook for people with the mutation.

Midostaurin (Rydapt) was the first drug approved for FLT3, and the first new drug approved to treat AML in 40 years. Doctors give Rydapt together with chemotherapy drugs such as cytarabine and daunorubicin.

You take Rydapt by mouth twice a day. It works by blocking FLT3 and other proteins on leukemia cells that help them grow.

A study of 717 people with the FLT3 gene published in The New England Journal of Medicine looked at the effects of treatment with this new drug. Researchers found that adding Rydapt to chemotherapy prolonged survival compared to an inactive treatment (placebo) plus chemotherapy.

The four-year survival rate was 51 percent among people who took Rydapt, compared to just over 44 percent in the placebo group. The average length of survival was more than six years in the treatment group, versus just over two years in the placebo group.

Rydapt can cause side effects such as:

  • fever and low white blood cells (febrile neutropenia)
  • nausea
  • vomiting
  • sores or redness in the mouth
  • headaches
  • muscle or bone pain
  • bruises
  • nosebleeds
  • high blood sugar levels

Your doctor will monitor you for side effects while you’re on this drug, and offer you treatments to help manage them.

A few other FLT3 inhibitors are still in clinical trials to see if they work. These include:

  • crenolanib
  • gilteritinib
  • quizartinib

Researchers are also studying whether a stem cell transplant after treatment with an FLT3 inhibitor might reduce the chance of the cancer coming back. They’re also looking at whether different combinations of drugs might be more effective in people with this mutation.

Having the FLT3 mutation if you have AML used to mean having a poorer outcome. Now, drugs like Rydapt are helping to improve the outlook. New drugs and combinations of drugs may extend survival even more in the years to come.

If you’re diagnosed with AML, your doctor will test your cancer for FLT3 and other gene mutations. Knowing as much as possible about your tumor will help your doctor find the most effective treatment for you.