Tyrosine kinase inhibitors (TKI) for chronic myeloid leukaemia (CML)
The main treatment for chronic myeloid leukaemia (CML) uses drugs called tyrosine kinase inhibitors (TKIs).
TKIs are a type of targeted therapy. They work by switching off (inhibiting) the tyrosine kinase made by the BCR-ABL1 gene in leukaemia cells. This slows or stops the bone marrow from making abnormal white blood cells. It also allows the leukaemia cells to mature and die.
There are many different TKIs for CML. They come as tablets that you take every day. If a TKI does not work, or stops working, you can usually be switched to a different one.
The three main TKI drugs currently used for CML are:
Nilotinib can be used as a first treatment in the chronic phase. It can also be used in the chronic or accelerated phase if you cannot have imatinib because of side effects or if it is not working to control the CML.
Dasatinib can be used as a first treatment in the chronic phase. It can also be used in the chronic, accelerated or blast phase if imatinib is causing severe side effects or is not working to control the CML.
There are also some newer TKI drugs, such as
Ponatinib may be used for people who have leukaemia cells with a particular gene change (mutation) called T3151. Only a few people with CML have this gene change in their leukaemia cells. You may be offered ponatinib if you have tried other TKI treatments but they have stopped working. Or you had to stop taking them because of side effects.
Different drugs are used for different situations. Your haematologist will discuss which one is appropriate for you.
Although the TKIs are similar, they work in slightly different ways. This means they can have different side effects. To make sure the TKI you have is right for you, your doctor will think about:
- any health problems you have
- the possible side effects of the TKI.
If a drug is not available on the NHS, there may be different ways you can still have it. Some people may be given it as part of a clinical trial. Your doctor can give you advice. We also have information on what to do if a drug is not available.
The side effects of TKIs are usually mild and treatable. Side effects are often more noticeable when you first start treatment, and they may improve with time.
If you have severe side effects, your doctor may ask you to stop taking the drug for a few days. After a short break, you may be able to start taking it again without having the same problems. Occasionally people need to stop treatment with the TKI they are taking because their side effects are too severe. If this happens, they will usually be offered a different TKI drug.
Sometimes a new side effect can develop many months after you started treatment. Always let your doctor know if you notice any new side effects or if your side effects get worse.
Each TKI can have slightly different side effects, so it is best to read our specific information about the drug you are having.
Because TKIs are a newer type of drug, there is not a lot of information available yet about getting pregnant or making someone pregnant while taking TKIs.
Taking a TKI during pregnancy increases the risk of harm to a developing baby. Because of this, you are strongly advised to use contraception while being treated with a TKI. If you think you may want to have children in the future, talk to your doctor about this as soon as possible. They can talk to you about the possible options for planning your treatment. They will aim to make things as safe as possible for you and any future pregnancy. If you think you may have become pregnant while taking a TKI, discuss this with your doctor as soon as possible. This is because the highest risk to the baby is during the first few weeks of the pregnancy.
There is less evidence about making someone pregnant while taking a TKI. But you should still talk to your doctor if you are planning to have a baby. The advice may be different depending on which type of TKI you are having.
When you first start treatment with a TKI, you will need to go to the clinic every 1 to 2 weeks. This is so your doctors can closely monitor how well treatment is working, and to check for any side effects. As time goes on, you will not need to go as often. Eventually, you may only need a check-up every 3 to 6 months.
At these check-ups, your doctor will:
- ask about your general health
- ask about any new symptoms or side effects from treatment
- do blood tests to check the numbers of blood cells (FBC) and leukaemia cells (PCR test).
Sometimes they may also take a bone marrow sample. Your doctor can tell you how often you might need this.
The results of these tests help your doctors know how well the treatment is working to control the leukaemia. This means they can make any changes if needed.
The aim of treatment is to put CML into remission. In CML, remission means there are no signs of CML in your blood during a standard blood test. But this does not mean the leukaemia has completely gone. You will need to keep taking treatment to keep the leukaemia in remission. Because there are still leukaemia cells, doctors may use the word response instead of remission.
There are different levels of remission (response). These are based on the results of different tests that look for leukaemia cells as the leukaemia responds to treatment.
When you first develop CML, your number of white blood cells is usually high. If there is a haematological response, it means your full blood count has returned to normal and no leukaemia cells can be seen. If your spleen was enlarged, it has gone back to its normal size.
Most people get a haematological response within three months of starting a TKI.
This is the next level of response. It refers to the amount of Philadelphia chromosome in the blood and bone marrow. As treatment starts working, the number of Philadelphia chromosome-positive (Ph+) cells in the blood and bone marrow goes down.
To check for a cytogenetic response, you have a bone marrow sample taken. Your doctors will usually examine at least 20 cells from the sample to see if there has been a cytogenetic response. There are different levels of cytogenetic response, depending on the amount of Ph+ cells in the bone marrow.
It takes longer to get a cytogenetic response than a haematological response. It sometimes takes many months.
About 8 out of 10 people taking imatinib for CML in the chronic phase (80%) get a complete cytogenetic response. This means there are no Ph+ cells detected in the bone marrow sample.
Even after you have a cytogenetic response, there can still be leukaemia cells in your blood and bone marrow. Because there may only be one leukaemia cell among thousands of normal blood cells, a very sensitive test is needed to find the leukaemia cells.
The PCR test can detect 1 leukaemia cell in 10,000 normal blood cells. It does this by measuring a substance made by the BCR-ABL1 gene in the leukaemia cells.
When you are first diagnosed with CML, you will have blood taken for a PCR test. After diagnosis, you will have this done every three months. Because it is so sensitive, the PCR test may keep showing signs of leukaemia for many months after your treatment starts, even though you are feeling well.
There are two different levels of molecular response:
- If you have a major molecular response, it means there are tiny amounts of the BCR-ABL1 gene in the blood.
- If you have molecularly undetectable leukaemia, the PCR test cannot detect any of the BCR-ABL1 gene in your blood.
You will need to keep taking the TKI for as long as it is controlling the leukaemia. This is important even if your PCR tests do not show any signs of leukaemia.
If you find it difficult to remember to take your tablets every day, you may find the following ideas helpful:
- Take your tablets at the same time each day.
- Put your tablets in a place where you will see them every day (but keep them out of sight and reach of children).
- Mark off each dose you take on a calendar.
- Keep a supply of tablets with you when you travel, and take your medicine in your carry-on luggage when you fly.
Your prescriptions will be organised through the hospital, so you may have to go there to collect the tablets each time you need more. Tell your doctor, nurse or pharmacist if it is difficult for you to get to the hospital.
There are trials currently looking at whether it may be safe to stop TKI treatment if someone has had molecularly undetectable leukaemia for a long time. This is not recommended at the moment, but if someone is finding side effects too difficult, it may occasionally be done. In the future, it may become more common practice, depending on the results of the trials.
If you have questions about this, you can talk to your doctor.
Below is a sample of the sources used in our chronic myeloid leukaemia (CML). If you would like more information about the sources we use, please contact us at firstname.lastname@example.org
European Leukemia Net. Recommendations for the management of chronic myeloid leukemia. 2013.
Hoffbrand V, and Moss P. Hoffbrand’s essential haematology. 7th edition. 2016.
National Institute for Health and Care Excellence. Leukaemia (chronic myeloid) – dastatinib, nilotinib and standard dose imatinib for the first-line treatment of chronic myeloid leukaemia (part review of technology appraisal guidance 70). April 2012.
National Institute for Health and Care Excellence. Technology appraisal guidance. 401/426/425.
DeVita V, Lawrence T and Rosenberg S. 2016. Lymphomas and leukemias. From Cancer: principles and practice of oncology.
This information has been written, revised and edited by Macmillan Cancer Support’s Cancer Information Development team. It has been reviewed by expert medical and health professionals and people living with cancer. It has been approved by Senior Medical Editor, Dr Anne Parker, Consultant Haematologist.
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