Tyrosine kinase inhibitors (TKIs)

TKIs are classed as a targeted therapy. They work by stopping your cells from producing a protein called a tyrosine kinase, which is made by the abnormal BCR::ABL1 gene in the Philadelphia chromosome.

This protein causes leukaemia cells to divide more quickly and live longer than healthy blood cells. If left untreated, these cancer cells would continue to crowd out your blood and bone marrow and the disease would get worse.

When you’re first diagnosed, your hospital team will discuss which TKI is best for you. The treatment they recommend is known as your first line treatment. Most people start on imatinib, which was the first TKI to be developed over twenty years ago. Since then, lots more have become available in the UK. One of them may be more suitable for you than others, and your doctor will explain why they recommend a particular TKI.

If the first TKI you try stops working for you or becomes less effective, your doctor will suggest trying a different one. You might also be able to switch to a different TKI if you find the side effects of the one you’re on too difficult to cope with. This is known as your second line treatment, and you may be able to repeat this process more than once.

Your doctor may be able to tell you why you tolerate one TKI better than another, or they might not know. It’s important to remember that there are lots of options to try, and that if one TKI is not the right treatment for you, there are alternatives.

If you struggle to tolerate at least two different TKIs, your doctor may recommend trying a newer or different type of TKI. One example is a TKI called asciminib. You can read more about the different types of TKI below.

There are lots of different types of TKI approved for use in the UK, and scientists are researching even more. The TKI you are given first will depend on what phase of CML you have, as well as things like your age, the potential risk of side effects, and any other conditions you have.

The TKIs currently approved for use in the UK are:

It’s important to take your TKI exactly how your doctor tells you to (this is sometimes referred to as your regimen). Evidence shows that if you do, you’re more likely to have a better response to the treatment.

Some people find it tricky to adapt to taking TKIs, especially if they are advised to plan their mealtimes around the medication. You might find it helpful to set alarms to remind yourself when to have a tablet. You could also experiment with adjusting what and when you eat, such as swapping breakfast and lunch for a bigger brunch, or snacking more in the evening so you're less hungry when you wake up.

It’s important to avoid eating grapefruit, drinking grapefruit juice, or taking antacids such as Gaviscon or Rennies whilst you’re on a TKI. This is because they can affect how your body absorbs the treatment.

TKIs may also interact with treatment for other common conditions, including over-the-counter medication. It is therefore very important to tell your hospital team about any regular medication you take. They will check there are no interferences, which may increase the side effects you experience or reduce the chance of your TKI working properly.

Whilst a lot of people will have to take TKIs for life, research suggests that it can be safe for some to taper (reduce) their dose, have a treatment break, or sometimes even stop taking their tablets entirely.

Treatment breaks can also help to manage side effects, and are something you might be able to look into if you’re planning to have a baby.

You can ask your hospital team about whether or not they think you can stop or pause treatment. They will consider your individual circumstances and discuss the benefits and risks with you. Remember, it may not be possible for everyone to explore this option.

If you are able to come off treatment permanently or for a short period of time, you will be regularly monitored by your team. These check-ups might occur every few weeks at first, and then change to less often depending on your results. You might hear this period of time referred to as "active monitoring".

Sometimes, your doctor or nurse may bring up stopping treatment themselves. It can be hard to understand what this might mean for you, and some people struggle with the idea of changing a routine that works for them. Others worry that their CML will get worse again as soon as they come off their tablets. You can express your own wishes at any time, and if you don’t want to stop taking a TKI that’s working for you, you don’t have to.

It’s also important to know that if you completely stop taking a TKI, you may have to go on a different one if you need more treatment in the future. If you taper a TKI, it should be possible to increase the dose of the same TKI again if needed.