Targeted Therapies for Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) cells contain an oncogene, BCR-ABL, that isn't found in normal cells. This gene makes a protein, BCR-ABL, which causes CML cells to grow and reproduce out of control. BCR-ABL is a type of protein known as a tyrosine kinase. Drugs known as tyrosine kinase inhibitors (TKIs) that target BCR-ABL are the standard treatment for CML. These include:

  • Imatinib (Gleevec)
  • Dasatinib (Sprycel®)
  • Nilotinib (Tasigna®)
  • Bosutinib (Bosulif®)
  • Ponatinib (Iclusig®)

All of these drugs can have serious or even deadly interactions with other drugs, over the counter supplements, and even certain foods (such as grapefruit and pomegranate). Be sure that your doctor always has an up-to-date list of any medicines you are taking, including over-the-counter medicines, vitamins, and herbal supplements. You also need to check with your doctor before starting any new medicine, to be sure it is safe.

It is also important to understand that all of the TKIs can harm the fetus if taken during pregnancy. These drugs seem to work best on CML that is still in the chronic phase, but they also can help patients with more advanced disease for some time.


Imatinib (Gleevec) was the first drug to specifically target the BCR-ABL tyrosine kinase protein, and it quickly became the standard treatment for CML patients. Because it was the first TKI, imatinib is known as a first generation tyrosine kinase inhibitor.

Almost all CML patients respond to treatment with imatinib, and most of these responses seem to last for many years. This drug doesn't seem to make the leukemia go away and stay away, so patients need to take it indefinitely (or until it stops working). Imatinib is taken by mouth as a pill with food, usually once a day.

Common side effects can include diarrhea, nausea, muscle pain, and fatigue. These are generally mild. About 30% of people taking the drug have itchy skin rashes. Most of these symptoms can be treated effectively, if needed.

Another common side effect is fluid buildup around the eyes, feet, or abdomen. In rare cases the fluid may collect in the lungs or around the heart, which can cause trouble breathing. Some studies have suggested that some of this fluid buildup may be caused by effects of the drug on the heart, though this is rare. It's not yet clear how serious this is or if it might go away if treatment is stopped. If you are taking this drug, tell your doctor right away if you notice sudden weight gain or fluid buildup anywhere in the body or have trouble breathing.

Another possible side effect is a drop in a person's white blood cell and platelet counts. When this happens at the beginning of treatment, it might be because the blood-forming cells that are making these are part of the malignant process. If this is the case, normal blood-forming cells take over and the blood counts will begin to rise to normal over time.

Your doctor might tell you to stop taking the drug for a short period if your blood counts get too low. This can also happen later on in treatment. In the past, low red blood cell counts were treated with a red cell growth factor, such as erythropoietin (Procrit®) or darbepoietin (Aranesp®), but these drugs are used less often now. Instead, your doctor may lower the dose of imatinib to see if your blood counts improve.

In some patients, imatinib eventually seems to stop working. This is known as imatinib resistance. Resistance to imatinib seems to be caused by changes in the genes of the CML cells. Sometimes this resistance can be overcome by increasing the dose of imatinib, but some patients need to change to a different drug, such as one of the other TKIs described further on.


Dasatinib (Sprycel) is another tyrosine kinase inhibitor that targets the BCR-ABL protein. Because it was developed after imatinib, it is called a second generation TKI. Like imatinib, this drug is a pill taken by mouth.

Dasatinib can be used as the first treatment for CML, but it can also be helpful for patients who can’t take imatinib because of side effects or because imatinib isn’t working.

When it was first approved, dasatinib was a pill taken twice a day, but more often now a larger dose is taken once a day.

The possible side effects of dasatinib seem to be similar to those of imatinib, including fluid buildup, lowered blood cell counts, nausea, diarrhea, and skin rashes. A serious side effect that can occur with this drug is fluid buildup around the lung (called a pleural effusion). This side effect is more common in patients taking this drug twice a day. The fluid can be drained off with a needle, but it can build up again, and may require the dose of dasatinib to be decreased.


Nilotinib (Tasigna) is another second generation TKI that targets the BCR-ABL protein. Like dasatinib, this drug can be used as a first treatment for CML, as well as for use in people who can’t take imatinib or whose CML no longer responds to it.

Side effects of nilotinib seem to be mild, but can include fluid buildup, lowered blood cell counts, nausea, diarrhea, and some lab test abnormalities. It can cause high blood sugar and pancreatitis, although this is rare.

This drug can also affect the rhythm of the heart, causing a condition called prolonged QT syndrome. This usually doesn't cause any symptoms, but can be serious or even fatal. This is why patients should have an electrocardiogram (EKG) before starting nilotinib and then again while being treated. This heart rhythm problem can sometimes be caused by nilotinib interacting with other drugs or supplements, so it's especially important to be sure that your cancer doctor knows about any medicines you take, including over-the-counter medicines and supplements. You also need to check with your doctor before starting any new medicine, to be sure it is safe.


Bosutinib (Bosulif®) is another TKI that targets the BCR-ABL protein. At this time, this drug is only approved by the US Food and Drug Administration to treat patients after they have been treated with another TKI.

Common side effects are usually mild and include diarrhea, nausea, vomiting, abdominal pain, rash, fever, fatigue, and low blood cell counts (including low platelet counts, low red blood cell counts, and low white blood cell counts). Less often, this drug can also cause problems with fluid retention, liver damage, and severe allergic reaction. Your doctor will check your blood test results regularly to watch for problems with your liver and low blood counts.


Ponatinib (Iclusig®) is a new TKI targeting the BCR-ABL protein. Because of risks of some serious side effects, this drug is only used to treat patients with CML if all of the other TKIs don’t work or if their leukemia cells have a certain gene change called the T315I mutation. This mutation (gene change) occurs in the leukemia cells of some CML patients who are treated with a TKI, and it prevents other TKIs from working. Ponatinib is the first TKI to work against CML cells that have this mutation.

This drug is a pill taken once a day.

Most side effects are mild and can include abdominal (belly) pain, headache, rash or other skin problems, and fatigue.

High blood pressure is also fairly common, and it may need to be treated with a blood pressure drug.

There is also a risk of serious blood clots that can lead to heart attacks and strokes, or block arteries and veins in the arms and legs. Rarely, blood clots in patients taking this drug have cut off circulation, and lead to an arm or leg needing to amputated (cut off). Surgery or some other procedure may be needed to treat these blood clots. The risk of serious blood clots is higher in older patients, those with certain risk factors, such as high blood pressure, high cholesterol, or diabetes, and those who have already had a heart attack, stroke, or poor circulation.

More rarely, this drug can also weaken the heart muscle, leading to a condition known as congestive heart failure. It can also cause liver problems, including liver failure, as well as pancreatitis (inflammation of the pancreas, which can lead to severe belly pain, nausea, and vomiting).

For general information about targeted therapy, see Targeted Therapy.

The American Cancer Society medical and editorial content team

Last Medical Review: February 24, 2015 Last Revised: February 22, 2016

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