Targeted Therapy Drugs for Acute Myeloid Leukemia (AML)

In recent years, drugs that target specific parts of cancer cells have been developed. Targeted drugs work differently from standard chemotherapy (chemo) drugs and tend to have different side effects. They can sometimes be helpful even when chemo isn’t, or they can be used along with chemo to help it work better.

Some of these drugs can be useful in treating certain people with acute myeloid leukemia (AML).

FLT3 inhibitors

In some people with AML, the leukemia cells have a mutation in the FLT3 gene. This gene helps the cells make a protein (also called FLT3) that helps the cells grow. Drugs that target the FLT3 protein can help treat some of these leukemias.

Midostaurin (Rydapt) is a drug that works by blocking FLT3 and several other proteins on cancer cells that can help the cells grow. This drug can be used along with certain chemotherapy drugs to treat newly diagnosed adults whose leukemia cells have a mutation in the FLT3 gene. Your doctor can test your blood to see if you have this mutation.

Midostaurin is taken by mouth twice a day.

Common side effects can include low levels of white blood cells (with increased risk of infection), fever, nausea, vomiting, redness or sores in the mouth, headache, muscle or bone pain, bruising, nosebleeds, high blood sugar levels, and upper respiratory infections.

Less often, this drug can cause serious lung problems, which might show up as a cough, chest pain, or shortness of breath. Tell someone on your cancer care team right away if you have any of these symptoms.

Gilteritinib (Xospata) is another drug that works by blocking FLT3 and other proteins on cancer cells that can help the cells grow. This drug can treat adults whose leukemia cells have a mutation in the FLT3 gene and whose AML has not gotten better on previous treatments or has recurred (come back). Your doctor can test your blood to see if you have this mutation.

Gilteritinib is taken by mouth once a day.

Common side effects can include fever, shortness of breath, diarrhea, swelling, redness or sores in the mouth, muscle or bone pain, fatigue, abnormal liver tests, and pneumonia (lung infection).

Less often, this drug may cause serious heart problems, which might show up as an abnormal electrocardiogram (ECG), or neurological problems which may show up as seizures or confusion. Tell someone on your cancer care team right away if you have any of these symptoms.

A rare but serious possible side effect of this drug is known as differentiation syndrome. This occurs when the leukemia cells release certain chemicals into the blood. It most often occurs during the first treatment cycle. Symptoms can include fever, breathing problems from fluid buildup in the lungs and around the heart, low blood pressure, liver or kidney damage, and severe fluid buildup elsewhere in the body. It can often be treated by stopping the drug for a while and giving a steroid such as dexamethasone.

IDH inhibitors

In some people with AML, the leukemia cells have a mutation in the IDH1 or IDH2 gene. These genes help the cells make certain proteins, which are also called IDH1 and IDH2. Mutations in one of these genes can stop blood cells from maturing the way they normally would.

Targeted drugs called IDH inhibitors can block these IDH proteins. These drugs seem to work by helping the leukemia cells mature (differentiate) into more normal cells. Because if this, they are sometimes referred to as a differentiation agents.

These drugs can be used to treat AML with an IDH1 or IDH2 mutation. Your doctor can test your blood or bone marrow to see if your leukemia cells have one of these mutations.

  • Ivosidenib (Tibsovo) is an IDH1 inhibitor. It can be used to treat AML with an IDH1 mutation, either as the first treatment in people who are older or are not healthy enough to tolerate strong chemo, or to treat AML that comes back after treatment or is no longer responding to other treatments.
  • Enasidenib (Idhifa) is an IDH2 inhibitor. It can be used to treat AML with an IDH2 mutation, either as the first treatment in people who are older or are not healthy enough to tolerate strong chemo, or to treat AML that comes back after treatment or is no longer responding to other treatments. 

These drugs are taken by mouth, once a day.

Common side effects can include nausea, vomiting, diarrhea, fatigue, joint pain, shortness of breath, increased levels of bilirubin (a substance found in bile), and loss of appetite. 

An important possible side effect of these drugs is known as differentiation syndrome. This occurs when the leukemia cells release certain chemicals into the blood. It most often occurs during the first treatment cycle. Symptoms can include fever, breathing problems from fluid buildup in the lungs and around the heart, low blood pressure, liver or kidney damage, and severe fluid buildup elsewhere in the body. It can often be treated by stopping the drugs for a while and giving a steroid such as dexamethasone.

Gemtuzumab ozogamicin (Mylotarg)

This targeted therapy consists of a monoclonal antibody (a man-made immune protein) linked to a chemotherapy drug. The antibody attaches to a protein called CD33, which is found on most AML cells. The antibody acts like a homing signal, bringing the chemo drug to the leukemia cells, where it enters the cells and kills them when they try to divide into new cells.

This drug can be used along with chemotherapy as part of the initial treatment of AML that has the CD33 protein. It can also be used by itself, either as the first treatment (especially in people who might not be healthy enough for intense chemo), or if other treatments are no longer working. It is given as an infusion into a vein (IV).

The most common side effects are fever, nausea and vomiting, low levels of blood cells (with increased risks of infection, bleeding, and fatigue), swelling and sores in the mouth, constipation, rash, and headaches.

Less common but more serious side effects can include:

  • Severe liver damage, including veno-occlusive disease (blockage of veins in the liver)
  • Reactions during the infusion (similar to an allergic reaction). You will likely be given medicines before each infusion to help prevent this.
  • Serious or life-threatening infections, especially in people who have already had a stem cell transplant
  • Changes in the rhythm of the heart

BCL-2 inhibitor

Venetoclax (Venclexta) targets BCL-2, a protein in cancer cells that helps them live longer than they should. This drug can be used with chemotherapy in people with newly diagnosed AML who are 75 years or older, or who are not healthy enough to tolerate strong chemo. It's taken by mouth once a day.

Side effects can include low levels of certain white blood cells (neutropenia), low red blood cell counts (anemia), diarrhea, nausea, bleeding, low platelet counts (thrombocytopenia), and feeling tired. Less common but more serious side effects can include pneumonia and other serious infections.

Tumor lysis syndrome (TLS) is another possible side effect of this drug. It's more common in patients who have large numbers of leukemia cells in their body when treatment starts. When the leukemia cells are killed, they break open and release their contents into the bloodstream. This can overwhelm the kidneys to the point that they get rid of all of these substances quickly. This can lead to the build-up of too many minerals in the blood and even kidney failure. The excess minerals can also cause problems with the heart and nervous system. To help keep this from happening, you may start at a very low dose and then slowly increase it over time. Sometimes, other medicines may be given to help drop your white blood cell count below a certain level before starting this drug. Your treatment team will do blood tests and also watch for signs of TLS.

Hedgehog pathway inhibitor

AML cells can have mutations (changes) in genes that are part of a cell signaling pathway called hedgehog. The hedgehog pathway is crucial for the development of the embryo and fetus and is important in some adult cells, but it can be overactive in leukemia cells.

Glasdegib (Daurismo) is a drug that targets a protein in this pathway. It can be used with chemotherapy in people with newly diagnosed AML who are 75 years or older, or who are not healthy enough to tolerate strong chemo. In this group, it has been shown to help people live longer.

This drug is taken by mouth once a day.

Side effects can include muscle and bone pain, fatigue, low white blood cell counts (neutropenia), low red blood cell counts (anemia), bleeding, nausea, low platelet counts (thrombocytopenia), and redness or sores in the mouth.  

Because the hedgehog pathway affects fetal development, these drugs should not be taken by women who are pregnant or could become pregnant. It is not known if they could harm the fetus if taken by a male partner. Anyone taking these drugs should use reliable birth control during and for some time after treatment.

To learn more about targeted therapy drugs as a treatment for cancer, see Targeted Cancer Therapy.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Larson RA. Induction therapy for acute myeloid leukemia in younger adults. UpToDate. 2018. Accessed at www.uptodate.com/contents/induction-therapy-for-acute-myeloid-leukemia-in-younger-adults on June 20, 2018.

National Comprehensive Cancer Network. NCCN Practice Guidelines in Oncology: Acute Myeloid Leukemia. V.1.2018. Accessed at www.nccn.org/professionals/physician_gls/pdf/aml.pdf on June 20, 2018.

Last Medical Review: August 21, 2018 Last Revised: May 30, 2019

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