Treating chronic myeloid leukaemia (CML) with TKIs

The main treatment for chronic myeloid leukaemia (CML) is with drugs called tyrosine kinase inhibitors (TKIs).

TKIs are a type of targeted therapy. They work by switching off (inhibiting) the tyrosine kinase that is made by the BCR-ABL1 gene in the leukaemia cells. This stops or slows the bone marrow from making abnormal white blood cells. It also allows the leukaemia cells to mature and die..

The TKI drugs used to treat CML come as tablets or capsules. You take them every day for as long as they are working. The three main TKI drugs currently used are:

  • Imatinib

    Imatinib is the most commonly used TKI for CML. It can be used in any phase.

  • Nilotinib

    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. This might be because of side effects or if imatinib is not working.

  • Dasatinib

    Dasatinib can be used as a first treatment in the chronic phase. It can also be used in any phase if imatinib is causing severe side effects or is not working to control the CML.

There are also some newer TKI drugs:

  • Bosutinib

    You might have bosutinib if other TKIs have stopped working or are not suitable for you.

  • Ponatinib

    Your doctors may prescribe ponatinib if you have leukaemia cells with a gene change (mutation) called T3151. Only a few people with CML have this gene change in their leukaemia cells.

    You may also be offered ponatinib if other TKIs have stopped working, or if you had to stop taking them because of side effects.

Different drugs are used for different situations. Your haematologist will discuss which one is best for you.

Although the TKIs are similar, they can have different side effects. To make sure the TKI you have is right for you, your haematologist will think about:

  • any other 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.

TKI and Hepatitis B and C

Before you begin treatment with a TKI, you will have a blood test to check for hepatitis B and C (liver infections). This is because TKI treatment can make these infections active again. Your doctor or nurse will talk to you about this before the blood test.

Side effects of TKIs

The side effects of TKIs are usually mild and treatable. Side effects are often more noticeable when you first start treatment and may get better over 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. Sometimes, people need to stop treatment with the TKI they are taking because their side effects are too severe. If this happens, you will usually be offered a different TKI drug.

Sometimes a new side effect can develop many months after you started treatment. Always tell your doctor if you notice any new side effects, or if your side effects get worse.

Each TKI has slightly different side effects, so it is best to read specific information about the drug you are having.

Contraception and fertility with TKIs

Because TKIs are a newer type of drug, there is limited information available about becoming pregnant or getting someone pregnant while taking TKIs. But TKIs are not thought to affect your fertility (your ability to become pregnant or make someone pregnant).

If you may want to have children in the future, talk to your doctor about this as early as possible – before starting treatment if you can. They may refer you to a specialist CML unit or fertility expert. They can talk to you about the possible options for planning your treatment.

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 have become pregnant while taking a TKI, tell your doctor as soon as possible. This is because the highest risk to the baby is during the first few weeks of the pregnancy. Your doctor can talk to you about the possible options for planning your treatment and controlling the CML. They will aim to make things as safe as possible for you.

There is less evidence about making someone pregnant while taking a TKI. Research has shown it may be safe to continue to take imatinib if you are trying to start a pregnancy. But there is less information about the newer TKI treatments. You should talk to your doctor before planning to have a baby. Their advice may be different depending on which TKI you are taking.

Monitoring response to TKI treatment

When you first start treatment with a TKI, you will be monitored by your healthcare team every 1 to 2 weeks.

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 take a bone marrow sample. Your doctor can tell you how often you might need this.

These test results help your doctors know how well the treatment is working to control the leukaemia. They will also check for any side effects. They can make any changes if needed.

As time goes on, you will not need to see your doctors as often. Eventually, you may only need a check-up every 3 to 6 months.


Levels of response to treatment in CML

The aim of treatment is to put chronic myeloid leukaemia (CML) into remission and keep it in remission. This means there are no signs of leukaemia in your blood during a standard blood test. It 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, your doctors may use the word response instead of remission.

There are different levels of response. These are based on the results of different tests that look for leukaemia cells as the leukaemia responds to treatment.

  • Haematological response

    A haematological response is the first level of response to treatment. It is measured with a full blood count. After you start treatment, you will have regular blood tests to check this response.

    When you first develop CML, the number of white blood cells in your blood is usually high. If there is a complete haematological response, it means:

    • your full blood count has gone back to normal
    • the doctors cannot see any leukaemia cells
    • if your spleen was large before starting treatment, it has gone back to a normal size.

    Most people get a complete haematological response (CHR) within 3 months of starting a TKI.

    Although your blood counts are normal, there may still be leukaemia cells that cannot be detected by a full blood count.

  • Cytogenetic response

    A cytogenetic response 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, a doctor or nurse will take a bone marrow sample. 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 can take many months.

    A complete cytogenetic response (CCyR) means there are no Ph+ cells detected in the bone marrow sample.

  • Molecular response

    Even after you have a cytogenetic response, there can still be leukaemia cells in your blood and bone marrow. The doctors use a test called a polymerase chain reaction (PCR) test to find any leukaemia cells. It is a very sensitive test and can find single leukaemia cells among thousands of normal blood cells. It measures a substance made by the BCR-ABL1 gene in the leukaemia cells.

    A PCR test is done with a blood test. You will have blood taken for a PCR test when you are first diagnosed with CML. After this, you will have a PCR test every 3 months.

    There are different levels of molecular response:

    • MR3, or major molecular response (MMR) – this means there are small amounts of the BCR-ABL1 gene in the blood. There is less than 1 leukaemia cell in every 1000 white blood cells.
    • MR4, or a deep molecular response (DMR) – this means there are tiny amounts of the BCR-ABL1 gene in the blood. There is less than 1 leukaemia cell in every 10,000 white blood cells.
    • MR4.5 – this means there are very tiny amounts of the BCR-ABL1 gene in the blood. There is less than 1 leukaemia cell in every 32,500 white blood cells.
    • MR5 – this means there are extremely tiny amounts of the BCR-ABL1 gene in the blood. There is less than 1 leukaemia cell in every 100,000 white blood cells.

Continuing with treatment

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 show very low levels of leukaemia.

Regularly missing a dose of TKI can affect how well the CML responds to treatment. Research has shown that missing as few as 3 doses a month lowers your chances of getting the best response to treatment.

The following tips may help you to remember to take your treatment every day:

  • Take your tablets at the same time each day.
  • Set a daily reminder on your mobile phone.
  • Put your tablets or capsules 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 or capsules 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 treatment each time you need more. Tell your doctor, nurse or pharmacist if it is difficult for you to get to the hospital.

Treatment free remission in chronic myeloid leukaemia (CML)

Treatment free remission (TFR) in chronic myeloid leukaemia (CML), is when you stop tyrosine kinase inhibitor (TKI) treatment after a time of remission.

Clinical trials have been done to see whether it may be safe to stop TKI treatment if someone has had a deep molecular response for a long time. The results suggest it may be safe for certain groups of people to stop treatment.

Treatment free remission may have potential benefits. This includes reducing side effects and avoiding possible long-term effects of taking TKIs. If you want to try to have a baby, knowing when it might be safe to stop TKIs may also help.

The clinical trials involved people who had ‘undetectable’ CML for many years. This means the leukaemia was in a deep molecular response called MR4. The people in the trials had been taking imatinib, nilotinib, or dasatinib.

In about half of people taking part in the trials, the leukaemia became detectable again after they stopped having treatment for a period of time. If this happened, the person started taking a TKI again – in most people the leukaemia then became undetectable again.

Who can have treatment free remission

TFR is not suitable for everyone. There are strict criteria that you need to meet before you might be suitable for TRF.

When you were first diagnosed, you would have discussed and planned your treatment with your multidisciplinary team (MDT). Your team will also be involved in decisions about treatment free remission. If TFR might be suitable for you, you may be referred to a specialist CML centre.

Your doctors will talk to you about the risks and the benefits of TFR before you agree to it. It is important that you fully understand these.

Before your doctors will consider TFR, you need to:

  • be at least 18 years old
  • have been diagnosed in the chronic phase of CML
  • have no history of accelerated or blast phase
  • have a typical BCR-ABL1 gene when tested by polymerase chain reaction (PCR) at diagnosis
  • have been taking a TKI for at least 3, and ideally 5, years
  • have had a deep molecular level of response on PCR testing of MR4 or better, for at least 2 years
  • be able to have frequent blood and PCR tests.

If you go ahead with TFR, you will need to have frequent blood tests. These are to make sure the CML is staying in remission.

You may experience muscle and joint pain or develop a rash when you stop TKI treatment. This is called TKI withdrawal syndrome. Most people find that it is mild and goes away by itself within 1 year. But sometimes it can last longer. You might feel anxious about needing to have frequent blood tests.

If, at any time, your blood tests show that the CML is coming back, you will need to start treatment with a TKI again. Usually the CML responds well to treatment in this case.

About our information

  • References

    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

    Smith G, Apperley J, Milojkovic D, et al. A British Society for Haematology Guideline on the diagnosis and management of chronic myeloid leukaemia. British Journal of Haematology, 2020; 191, 2, Available from [accessed on October 2020].

    Hochhaus A, Saussele S, Rosti G, et al. Chronic Myeloid Leukaemia: ESMO Clinical Practice Guidelines. Annals of Oncology, 2017; 28 (suppl 4), iv41-iv51. Available from [accessed on October 2020].

  • Reviewers

    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.

    Our cancer information has been awarded the PIF TICK. Created by the Patient Information Forum, this quality mark shows we meet PIF’s 10 criteria for trustworthy health information.

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Date reviewed

Reviewed: 01 December 2020
Next review: 01 December 2023

This content is currently being reviewed. New information will be coming soon.

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