Venetoclax (Venclyxto®) is a targeted drug that can make lymphoma cells undergo apoptosis (programmed cell death).
When cells are no longer needed, for example when they’re damaged, they die in a controlled way. This is called ‘apoptosis’ and it is a normal process within the body. Cancer can occur when there is a build-up of cells that survived when they should have died.
Venetoclax switches off the survival signals that keep some types of cancer cells alive when they should have died. This can make the cancer cells die.
- People with CLL that has certain genetic changes (17p deletion or TP53 mutation) and who can’t have a different type of targeted drug, a B-cell receptor pathway inhibitor (ibrutinib or idelalisib), or their condition didn’t respond to these drugs.
- People with CLL that didn’t respond to both chemo-immunotherapy (chemotherapy with antibody therapy) and a B-cell receptor pathway inhibitor (ibrutinib or idelalisib).
In combination with obinutuzumab, venetoclax is licensed for adults with CLL who have not had treatment before.
In combination with rituximab, venetoclax is also licensed for people with CLL who didn't respond to at least one previous treatment.
Venetoclax is being tested in further clinical trials in people with CLL to see if combining it with other treatments makes it more effective. It is also being tested in other types of lymphoma. Use our searchable database to see if there’s a clinical trial that might be suitable for you at Lymphoma TrialsLink.
Is it available on the NHS in the UK?
Venetoclax is available on the NHS throughout the UK on its own or in combination with rituximab, according to its licensed indications. In combination with obinutuzumab, venetoclax is available on the NHS throughout the UK for people with CLL who have not been treated before and either:
- have high-risk genetic mutations in their CLL cells
- do not have high-risk genetic mutations in their CLL cells but are not able to have treatment with the usual first-choice chemotherapy regimens used to treat CLL.
Venetoclax is becoming increasingly important as a treatment for CLL. It is currently used if other targeted drugs have failed to keep CLL under control.
Venetoclax gives high response rates and can completely clear CLL in some people – this is called a ‘complete remission’. A complete remission makes it more likely that your CLL will stay under control for a long time.
In the main clinical trial of 107 people with relapsed CLL and 17p deletion, three-quarters of people responded to treatment (their CLL was reduced or completely disappeared). In a clinical trial of 64 people with CLL who had previously taken idelalisib or ibrutinib, around two-thirds responded to treatment.
You take venetoclax as tablets once a day with a meal. You start at a low dose and the dose is gradually increased over the first 5 weeks of treatment. This reduces the number of CLL cells gradually. Killing too many cells at once can cause a serious side effect called ‘tumour lysis syndrome’, as your kidneys can struggle to remove the high levels of waste products from dying cells. Your dose may be reduced if you have troublesome side effects.
You keep taking venetoclax for as long as it is benefitting you and until your CLL stops responding to it. You may stop taking venetoclax earlier than this if you develop problematic side effects. This means you might continue to take venetoclax for several years, although some studies are testing whether venetoclax can be stopped after you have been in remission for a certain amount of time, without your CLL coming back.
All medicines can cause side effects (unwanted effects of treatment). As venetoclax is a new treatment, more information about possible side effects is still being gathered.
This is not a complete list of side effects that have been reported. Ask your medical team for the most up-to-date information about possible side effects. Ask all the questions you have. You also need to tell your medical team about any other conditions you have and any medicines, supplements or complementary therapies you are taking before you start any new treatment.
The most common side effects of venetoclax, which can affect more than 1 in 5 people, are:
- neutropenia (a drop in the number of neutrophils you have – a type of white blood cell that fights infection)
- gastrointestinal problems, such as nausea and vomiting, diarrhoea and constipation
- anaemia (a drop in the number of red blood cells you have)
- infections (for example, colds)
- abnormally high levels of phosphate in your blood, which might mean your kidneys are not working properly
- fatigue (extreme tiredness).
Less common but serious side effects can include:
- neutropenic sepsis (fever associated with neutropenia)
- serious infections like pneumonia.
Tumour lysis syndrome (TLS)
One possible complication of treatment with venetoclax is tumour lysis syndrome, which is problems caused by the rapid breakdown of cancer cells. To reduce the risk of TLS, your dose of venetoclax is increased gradually and you are monitored carefully.
- You should make sure you drink plenty of water before starting venetoclax and while your dose is being increased. Some people are given intravenous fluids (into a vein).
- You may be given other medications to reduce the risk of tumour lysis syndrome, or be monitored in hospital.
- You have regular blood tests so that tumour lysis syndrome can be detected quickly and venetoclax can be stopped. You might be able to restart venetoclax at the same dose or at a reduced dose.
Your medical team can give you further advice about fluid intake and reducing the risk of tumour lysis syndrome.
You might not be able to have venetoclax if you are taking other medications or have certain other conditions. Your doctor may reduce your dose and monitor you more closely or recommend that you do not take venetoclax if you have other conditions. These include liver problems and kidney problems. Your doctor might also change your dose if you experience troublesome side effects.
Certain drugs and foods can increase your risk of side effects during treatment with venetoclax.
- Drugs that affect an enzyme called CYP3A4: CYP3A4 acts on many drugs to help remove them from the body, including venetoclax. If you are taking a drug that interferes with the action of CYP3A4, it can decrease or increase the action of venetoclax, 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 such as St John’s Wort (used for depression and anxiety).
- Don’t drink grapefruit juice or eat grapefruit or Seville oranges (used in some types of marmalade). These can increase the amounts of venetoclax in your blood.
Venetoclax has not been approved for use in people under 18.
People who are pregnant should not usually have venetoclax during their pregnancy in case it could harm the unborn baby. Below are some recommendations you should follow.
- Prevent getting pregnant during treatment and for at least 30 days after finishing venetoclax treatment.
- Use a barrier method of contraception, like condoms. The effect of venetoclax on hormonal contraceptives, for example the pill, is unknown.
- Do not breastfeed if you are taking venetoclax.
Discuss your treatment options with your doctor if you think you might be pregnant.