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Chronic myeloid leukemia (CML) cells contain an abnormal gene, 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:
These drugs seem to work best when CML is in the chronic phase, but some can also help patients with more advanced disease (accelerated or blast phases). In most people, the TKIs don't seem to make the leukemia go away forever, so these drugs need to be taken indefinitely. But for some people who have very good, long-lasting responses to treatment, it might be possible to stop taking these drugs, or at least lower the dose. (See Treating Chronic Myeloid Leukemia by Phase to learn more.)
These drugs are pills you take at home. To get the best outcomes, it's important to take them exactly the way your doctor tells you to take them. Skipping pills or adjusting doses can effect the way TKI treatment works. See Oral Chemotherapy: What You Need to Know for more on how to best manage cancer treatments you take at home.
All of these drugs can have serious interactions with some other drugs, over-the-counter supplements, and even certain foods (such as grapefruit and pomegranates). Be sure that your doctor always has an up-to-date list of everything you're taking, including over-the-counter drugs, vitamins, and herbal supplements. You also need to check with your doctor before starting any new medicine, to be sure it's safe.
It's also important to understand that all of the TKIs can harm a fetus if taken during pregnancy.
Any of these TKIs might be used as the first (or frontline) treatment of chronic phase CML.
Imatinib (Gleevec) was the first drug to specifically target the BCR-ABL tyrosine kinase protein.
Almost all CML patients respond to treatment with imatinib, and most of these responses seem to last for many years.
Imatinib is taken by mouth as a pill with food, usually once a day.
Generic imatinib is also available. Studies have shown that it works as well as and causes the same kinds of side effects as the brand name, Gleevec.
Common side effects can include diarrhea, nausea, muscle pain, and fatigue. These are generally mild. Some people have itchy skin rashes. Most of these symptoms can be treated, if needed.
Another common side effect is fluid build-up around the eyes, feet, or abdomen (belly). 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 build-up 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 build-up anywhere in the body or have trouble breathing.
A person's white blood cell and platelet counts could possibly drop. When this happens at the beginning of treatment, it might be because the blood-forming cells that are making these are part of the leukemia process. If this is the case, normal blood-forming cells take over and the blood counts will begin to rise 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. Your doctor may lower the dose of imatinib to see if your blood counts improve.
In some patients, imatinib seems to stop working over time. 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.
Dasatinib (Sprycel) is another TKI that targets the BCR-ABL protein.
This drug is a pill taken once a day with or without food.
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.
The possible side effects of dasatinib seem to be similar to those of imatinib, including fluid build-up, lowered blood cell counts, nausea, diarrhea, and skin rashes.
A serious side effect that can occur with this drug is fluid build-up around the lung (called a pleural effusion). This side effect is more common in patients taking dasatinib twice a day. The fluid can be drained off with a needle, but it can build up again, and the dose of dasatinib may need to be decreased.
Nilotinib (Tasigna) is another TKI that targets the BCR-ABL protein. This drug can be used as a first treatment for CML, and is also used for people who can’t take imatinib or whose CML no longer responds to it.
It's taken as a pill. The patient cannot eat 2 hours before taking nilotinib and for 1 hour after taking it.
Side effects of nilotinib seem to be mild, but can include fluid build-up, lowered blood cell counts, nausea, diarrhea, rash, and some blood chemical changes that may need to be treated (for instance, low potassium and magnesium levels). It can cause high blood sugar and pancreatitis, but 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. Because of this, 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, vitamins, herbs, and supplements. You also need to check with your doctor before starting any new medicine, to be sure it's safe.
Bosutinib (Bosulif) is another TKI that targets the BCR-ABL protein. It can be used as the first treatment for CML, but most often it’s used if another TKI is no longer working.
This drug is taken as a pill with food once a day.
Common side effects are usually mild and include diarrhea, nausea, vomiting, abdominal (belly) 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 TKI targeting the BCR-ABL protein. Because this drug can cause some serious side effects, it's only used to treat patients with CML if all of the other TKIs don’t work or if their leukemia cells have a gene change called the T315I mutation. Ponatinib is one TKI to work against CML cells that have this mutation.
This drug is a pill taken once a day with or without food.
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's 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 another 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.
Less often, this drug can also weaken the heart muscle, leading to a condition known as congestive heart failure (CHF). 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).
Asciminib (Scemblix) is a TKI targeting a very specific area of the BCR-ABL protein. This drug is used to treat patients with chronic phase CML if two or more other TKIs have already been tried or if their leukemia cells have a gene change called the T315I mutation. Asciminib is another TKI to work against CML cells that have the T315I mutation.
This drug is a pill taken once a day or twice a day depending on the dose.
The most common side effects of asciminib include feeling tired, nausea, diarrhea, joint and muscle pain, skin rash, and infection of the upper airways. It might also cause some changes to your bloodwork such as a low platelet count, increased triglycerides, low white and red blood cell counts, and abnormal kidney function.
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.
Bristol-Myers Squibb. Highlights of prescribing information: Sprycel (dasatinib). 11/2017. Accessed at https://packageinserts.bms.com/pi/pi_sprycel.pdf on May 16, 2018.
Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring. Am J Hematol. 2018 Mar;93(3):442-459.
National Comprehensive Cancer Network, Clinical Practice Guidelines in Oncology (NCCN Guidelines®), Chronic Myeloid Leukemia, Version 4.2018 -- January 24, 2018. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/cml.pdf on May 16, 2018.
Novartis Pharmaceuticals Corporation. Highlights of prescribing information: Gleevec (imatinib mesylate). 9/2017. Accessed at www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/gleevec_tabs.pdf on May 16, 2018.
Pfizer Laboratories. Highlights of prescribing information: Bosulif (bosutinib). 12/2018. Accessed at labeling.pfizer.com/ShowLabeling.aspx?id=884 on May 16, 2018.
Takeda Pharmaceuticals Company Limited. Highlights of prescribing information: Iclusig (ponatinib). 12/2017. Accessed at iclusig.com/pi on May 16, 2018.
Last Revised: November 24, 2021
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