Innovative research has helped doctors learn more about how cancer cells grow and why it’s a bit different in every person. This has led to the development of drugs that target specific molecules that help cancer cells grow and spread.
Many people who receive a diagnosis of acute myeloid leukemia (AML) have a difference, or mutation, in the FLT3 gene. This gene instructs a protein receptor that’s important to cell growth.
New therapies called FLT3 inhibitors aim to target the FLT3 receptors in those with AML who have the gene mutation. The results are promising as a standalone therapy or when used along with chemotherapy for those who are candidates.
AML is a cancer of the bone marrow and blood. AML affects myeloblasts, a type of immature white blood cell made in the bone marrow.
In AML the myeloblasts are abnormal and don’t grow into healthy white blood cells. These abnormal white blood cells are also called leukemia blasts.
Abnormal cells can build up in the bone marrow and blood, leaving less room for healthy white blood cells, red blood cells, and platelets. This can lead to infection, anemia, and bleeding.
About one-third of people with newly diagnosed AML have a mutation in the FLT3 gene. This gene contains instructions for making a protein called FMS-like tyrosine kinase 3 (FLT3). This protein helps white blood cells grow.
The FLT3 protein belongs to a group of proteins called tyrosine kinase receptors. Biochemical processes happen when molecules attach to receptors on cells.
Tyrosine kinases are one class of these receptors that set off chains of events that are important to how cells grow and survive. Mutations in these receptors can lead to signaling that results in disease activity.
There is an excessive amount of FLT3 receptors on a majority of AML blasts. This may cause the body to make too many abnormal white blood cells.
Targeted therapies are a kind of precision medicine. They allow doctors to adjust a treatment so it’s more likely to work in a specific person due to their genes or other unique health factors.
Targeted therapies for cancer work by acting on the proteins that control how cancer cells grow and divide. This is different from chemotherapy, which works by killing rapidly growing cells.
Since chemotherapy drugs don’t know which cells are cancer and which are not, this treatment can also damage noncancerous cells, which can lead to side effects.
Targeted therapies may have different side effects than chemotherapy drugs. These side effects can vary depending on the type of drug given and what it targets.
Cancer cells can become resistant to targeted therapy. Doctors therefore may also recommend chemotherapy or radiation along with this form of treatment.
Drugs that target the FLT3 mutation are called FLT3 inhibitors.
There are several targeted therapies in development that focus on the FLT3 mutation. There are two therapies currently approved for use:
- Midostaurin (Rydapt) may be used alongside chemotherapy in people newly diagnosed with AML with the FLT3 mutation. It is taken orally twice a day. How often a person needs to take midostaurin may vary depending on what phase of treatment they’re in.
- Gilteritinib (Xospata) is also for people with the FLT3 mutation but is reserved for people whose cancer has come back or for whose cancer previous treatments did not work as hoped. It is taken orally once a day.
Both midostaurin and gilteritinib work by blocking FLT3 and other proteins that contribute to cancer cell growth.
In order for targeted therapy to work, the person with cancer must also
To see if you might be a candidate for FLT3 therapy, your doctor may want to test a blood or bone marrow sample for the presence of the FLT3 gene mutation.
Both midostaurin and gilteritinib come with possible side effects. Your doctor should speak to you about these before beginning treatment.
Possible side effects of midostaurin include:
- lung problems
- low white blood cell counts and fever (febrile neutropenia)
- mouth pain
- mouth ulcers
- muscle or bone pain
- high blood sugar (hyperglycemia)
- infection, including upper respiratory tract infection
Gilteritinib has several common side effects. These include:
- diarrhea, constipation, or nausea
- vomiting, dizziness, or headache
- cough or shortness of breath
- low blood pressure
- changes in liver function
- decreased urination
- swelling in the extremities (arms or legs)
- joint or muscle pain
- mouth or throat sores
- eye problems
There are also possible severe side effects that are less common, such as:
- differentiation syndrome, a condition that affects blood cells
- posterior reversible encephalopathy syndrome (PRES), a condition that affects the brain
- QTc prolongation, which is a change in the heart’s electrical activity
- pancreatitis, or inflammation of the pancreas
If you experience signs of severe side effects, your doctor may recommend attending your nearest emergency room.
Both midostaurin and gilteritinib have had favorable success rates in clinical trials.
A 2017 study on midostaurin involved 717 people with the FLT3 gene mutation. The 4-year survival rate was 51.4 percent for those in the midostaurin group compared to 44.3 percent of those in the placebo group.
Everyone in the study received both standard chemotherapy combined with either midostaurin or placebo.
- 8 percent had full remission
- 22 percent had full remission with incomplete platelet or hematological recovery
- 10 percent had partial remission
Sometimes targeted therapy can work well and then stop. Cancer cells can become resistant to the therapy, either because the target changes inside the body or the cancer cells find another way to grow.
If targeted therapy doesn’t work, or stops working, your doctor can explore other options. These may include other cancer treatments that do not involve the targeted therapy. Other treatment options for AML include:
- stem cell transplant
- clinical trials to try new treatments or new combinations of existing treatments
By using precision medicine, doctors can target treatments that are right for specific individuals and more likely to be effective.
Therapies for AML that target the FLT3 gene offer new hope to those that carry the gene difference. They hold great promise as a standalone therapy for those with relapsing AML or as a therapy used along with chemotherapy for those newly diagnosed.