Many newer treatments for lymphoma are targeted therapies. Such therapies aim to kill the type of cell that has turned cancerous or to stop signals that make cancerous cells grow or divide. Targeting treatment at a specific type of cell reduces its effects on other types of cell. This can diminish or even eliminate some of the side effects of chemotherapy, such as hair loss.
Cells receive signals that keep them alive and make them divide. These signals are sent along one or more pathways. Blocking either the signal or a key part of the pathway can make cells die or stop them from growing or dividing. Some signalling pathways are more important in certain types of lymphoma than in others. Scientists are trying to find out more about how various pathways are linked.
Ibrutinib (Imbruvica®) is a cell signal blocker that targets Bruton’s tyrosine kinase (BTK). BTK is a part of a pathway that helps B cells to stay alive and divide. Blocking BTK promotes death of B cells, including lymphoma cells that develop from B cells, and prevents their division. This stops the spread of lymphoma cells.
The European Medicines Agency (EMA) assesses drugs for use across Europe. Their assessment is then considered by the European Commission (EC) that makes the final decision on whether a drug should be granted a marketing authorisation (licence). Ibrutinib is approved in Europe for three types of lymphoma.
- For people whose lymphoma has relapsed (come back) or didn’t respond to treatment (refractory lymphoma). It is given on its own.
- As a first-line treatment.
- For people whose CLL has relapsed after treatment. It can be given on its own or with bendamustine and rituximab.
- For people who have previously received other treatments for WM. It is given on its own.
- For people who can’t have chemo-immunotherapy as first-line treatment. It is given on its own.
European approval to use ibrutinib in CLL and mantle cell lymphoma was granted in November 2014. It was then extended to WM in May 2015. In 2016, the EMA expanded ibrutinib’s recommended uses for CLL.
Ibrutinib is being tested in further clinical trials in people with these types of lymphoma. This is to see if ibrutinib could work better in combination with other treatments, such as chemotherapy or antibody therapy, eg rituximab. It is also being tested in other types of lymphoma. Find out if there’s a trial suitable for you at Lymphoma TrialsLink.
Once a drug has been approved in Europe, national authorities need to assess it to make a recommendation on funding. In the UK, health and technology assessment bodies decide whether to make drugs available on the NHS. These are:
- the National Institute for Health and Care Excellence (NICE), whose guidance is followed in England and Wales, and often in Northern Ireland if agreed by the Department of Health, Social Services and Public Safety
- the Scottish Medicines Consortium (SMC), and
- the All Wales Medicines Strategy Group (AWMSG), who look at some drugs before a decision is reached by NICE.
Ibrutinib is currently only available on the NHS for some people in certain parts of the UK.
- For people with relapsed or refractory CLL who can’t have treatments that include fludarabine.
- For people with CLL and a 17p deletion who can’t have chemo-immunotherapy.
- For people with relapsed or refractory mantle cell lymphoma.
In England and Wales
- For people with CLL who have had previous treatment or who have a 17p deletion or TP53 mutation and are not suitable for chemo-immunotherapy.
- Through the Cancer Drugs Fund for people with relapsed or refractory mantle cell lymphoma.
Ibrutinib is being assessed by NICE for other uses and NICE is expected to make further decisions on funding in 2017.
If you already have funding to cover the costs of ibrutinib on the NHS, it will continue even if NICE decides that the drug should not be routinely funded on the NHS.
If ibrutinib is approved for use in your situation but isn’t currently funded by the NHS, your doctor may be able to make an individual funding request in exceptional cases. Discuss this with your doctor if you think that this might apply to you.
If you have private medical insurance, ask your provider if they cover your treatment with ibrutinib.
Some people might be able to enter a clinical trial of ibrutinib. Ask your doctor if there is a clinical trial suitable for you or search for a trial at Lymphoma TrialsLink.
Ibrutinib is considered by many experts to be a ‘breakthrough treatment’ in some types of lymphoma. It gives higher response rates compared with other second-line therapies for the same types of lymphoma. Few people (5 in 100) treated with ibrutinib in clinical trials had to stop treatment because of side effects. The main trials that led to approval of ibrutinib are briefly described below.
Benefits in mantle cell lymphoma
Mantle cell lymphoma that has relapsed or not responded to first-line therapy can be difficult to treat. However, the main study in this area showed that more than two-thirds of 111 people treated with ibrutinib responded to the treatment (their lymphoma shrank or disappeared). A second study in 280 people compared ibrutinib with another cancer drug, temsirolimus, in people with relapsed or refractory mantle cell lymphoma. People lived for an average of 15 months without their lymphoma getting worse when treated with ibrutinib compared with an average of 6 months when treated with temsirolimus.
Benefits in Waldenström’s macroglobulinaemia (WM)
A high response rate has also been seen in people with WM – about 9 in 10 people with WM responded to ibrutinib treatment in a trial in 63 people. This trial led to the approval of ibrutinib for WM in Europe.
Benefits in chronic lymphocytic leukaemia (CLL)
Long-lasting responses have also been seen in CLL treated with ibrutinib. In the main trial involving 391 people with relapsed or refractory CLL, ibrutinib was compared with ofatumumab, which is often used for people with CLL that has come back. One year after starting treatment, around 66 in 100 people taking ibrutinib were still alive and their disease had not progressed (got worse) compared with around 6 in 100 people treated with ofatumumab.
In a second study involving 269 people who hadn’t yet received any treatment for their CLL, ibrutinib was compared with the chemotherapy drug chlorambucil. After 1.5 years of treatment, around 90 in 100 people taking ibrutinib were still alive and their disease had not progressed compared with around 52 in 100 people treated with chlorambucil.
Adding ibrutinib to bendamustine and rituximab for people with relapsed or refractory CLL was also effective in a study involving 578 people. The risk of CLL progressing was reduced by taking ibrutinib instead of a placebo (dummy treatment).
Ibrutinib is given as capsules. It is taken orally (by mouth). Always follow the advice of your doctor when taking ibrutinib. You can usually take the capsules at home. Make sure you know how many capsules you should take – your recommended dose of ibrutinib is based on the type of lymphoma you have and your general health.
- Swallow the capsules whole with a glass of water.
- Never open the capsules, break them or chew them.
- Take the capsules at about the same time every day.
- Check the information you are given to find out what you should do if you miss a dose.
When is ibrutinib given?
Ibrutinib capsules are taken once daily. They can be taken every day until your lymphoma stops responding unless side effects are bad enough to make you stop treatment. You might be treated with ibrutinib for years.
Keep taking ibrutinib for as long as your doctor tells you to, even if you feel well. If ibrutinib is keeping your lymphoma under control, the lymphoma could get worse if you stop taking the drug.
You will need to have blood tests to check your health, eg your blood cell counts, while you are taking ibrutinib. Your doctor might want you to have other tests depending on any other conditions you have or any side effects you develop. For example, you might have an electrocardiogram (ECG; a heart function test that records the rhythm and electrical activity of the heart) to check how well your heart is working. How often you need these tests depends on your individual circumstances such as other health conditions and how your lymphoma is responding.
Only the most common side effects are described on this page. This is not a complete list of side effects that have been reported. As ibrutinib is a new treatment, more information about possible side effects is still being gathered. Your team should discuss the most up-to-date information with you before you start treatment. Ask all the questions you have. Discuss with your medical team how ibrutinib might affect any other medical conditions you have.
Most side effects experienced by people treated with ibrutinib are mild. In clinical studies, few people (about 5 in 100) had to reduce their dose of ibrutinib because of side effects. A similar number (about 5 in 100) had to stop treatment for this reason.
The most common side effects of ibrutinib, which can affect more than 1 in 5 people, are:
- neutropenia (low neutrophils), which increases your risk of infection
- gastrointestinal effects: nausea, diarrhoea
- musculoskeletal pain (pain in muscles and bones)
- bruising and bleeding
Some of these risks are described in more detail below.
Although minor bleeding problems (eg bruising) are common, more serious events (eg a haemorrhage) can occur. Changes in heart rhythm can also present. These effects are described below.
Effects on blood
Ibrutinib can decrease the number of different types of cells in your blood. These effects are usually mild but can result in an increased risk of bleeding and developing infections. Ibrutinib can also cause a temporary increase in the number of lymphocytes (a type of white blood cell) in your blood. This does not normally cause any problems. Your medical team will check your blood cell counts regularly.
Ibrutinib can cause bleeding problems. These can be minor, eg bruising more easily, or serious, eg a haemorrhage. Bleeding problems could be caused by the effects of ibrutinib on platelet function. Platelets are found in your blood and help it to clot. It is not known why some people develop bleeding problems while others do not. People who take other drugs that affect platelets or drugs that thin the blood (anticoagulants such as warfarin) might not be able to take ibrutinib or may be monitored more carefully.
Tell your medical team if you notice any symptoms of bleeding problems: bloody or black stools (they look like tar), pink or brown urine, unexpected bleeding or bleeding that is severe or that you cannot control, vomiting blood or vomit that looks like coffee grounds, coughing up blood or blood clots, increased bruising, feeling dizzy or weak, confusion, changes in your speech, or a long-lasting headache.
Treatment with ibrutinib can lower your number of white blood cells. If you have low neutrophils (a type of blood cell that fights infection), this is called neutropenia and gives you a higher risk of getting an infection. Neutropenia with ibrutinib is generally mild. People treated with ibrutinib commonly get colds. More serious infections, eg pneumonia, can occur.
Some people treated with ibrutinib develop heart rhythm problems. This is more likely in people who are at a higher risk of heart problems or who have had them in the past. In many cases, you can continue taking ibrutinib if you develop changes in your heart rhythm but you may need to be monitored more carefully. Tell your medical team immediately if:
- you feel like your heart is beating quickly and irregularly
- you are light-headed, dizzy or faint
- you have shortness of breath or any discomfort in your chest.
Changes in the QT interval (a section of an ECG trace) have also occurred in some people treated with ibrutinib. It is not known whether these changes cause any problems. Your doctor will consider carefully whether ibrutinib is suitable for you if you already have changes in your QT interval or a relevant family history.
Some people will not be able to have ibrutinib because they are taking other medications or have other conditions. Make sure you tell your doctor about any medical conditions and any medicines you are taking. Your doctor may reduce your dose and monitor you more closely or recommend that you do not take ibrutinib if you have other conditions. These include liver problems, severe kidney problems or severe heart disease.
Some medications, including herbal remedies, can interact with ibrutinib and should not be taken with it. They could increase the risk of side effects or change the effect of ibrutinib. Give your doctor a list of all the medications you are taking. Make sure you include any vitamins, supplements or herbal remedies.
- Drugs that affect blood clotting: At the moment, it is not recommended that ibrutinib is given with warfarin. Ibrutinib can be given with some other medicines that thin your blood or stop it from clotting but you will need to be monitored carefully because of an increased risk of bleeding. You shouldn’t take certain vitamins and supplements, like fish oil or vitamin E.
- Drugs that act on an enzyme called CYP3A4: CYP3A4 acts on many drugs to help remove them from the body, including ibrutinib. If you are taking a drug that interferes with the action of CYP3A4, it can decrease or increase the action of ibrutinib, depending on how the drugs work together. It is important that your doctor knows about all the medications you are taking as there is a range of drugs that can have this effect, including some antibiotics and herbal remedies like St John’s Wort (used for depression and anxiety).
If you are about to have or have recently had surgery, you will not be able to take ibrutinib for at least 3 to 7 days before and after your operation, depending on the type of surgery recommended and your risk of bleeding.
Ibrutinib has not been approved for use in children. You must not take ibrutinib if you are pregnant or become pregnant as it could damage your unborn baby. Discuss your treatment options with your doctor if you think you might be pregnant.
Certain drugs and foods can increase your risk of side effects during treatment with ibrutinib.
- Tell your doctor if you are taking or would like to start taking any medications including, but not limited to, vitamins, supplements and herbal remedies.
- Don’t drink grapefruit juice or eat grapefruit or Seville oranges (used in some types of marmalade). These can increase the amounts of ibrutinib in your blood.
Report any side effects to your doctor as soon as possible. You might need to take action, eg to avoid infection. Your doctor might be able to give you medicine or advice to help with troublesome side effects.
- Follow your doctor’s advice if you have low blood counts.
- Do not drive or operate any machinery if you have side effects like fatigue or dizziness.
- Drink plenty of fluids. Diarrhoea is common in people taking ibrutinib but usually goes away after a couple of days. Tell your doctor if your diarrhoea does not go away in a couple of weeks.
Ibrutinib could damage an unborn baby or be passed to your baby in breast milk. Below are some recommendations you should follow.
- Prevent getting pregnant during treatment and for at least 3 months afterwards.
- Use a barrier method of contraception, like condoms. The effect of ibrutinib on hormonal contraceptives, eg the pill, is unknown.
- Do not breastfeed if you are taking ibrutinib.