Venetoclax + azacitidine

Your haematology team might recommend venetoclax + azacitidine for you if:

• You are newly diagnosed with AML AND
• Intensive chemotherapy is not suitable for you

Sometimes venetoclax may be given with other medicines instead of azacitidine, such as low-dose cytarabine. Your medical team will let you know which combination of medicines you are taking.

We have separate information about venetoclax for CLL or combined with other medicines.

Venetoclax

Venetoclax is a targeted medicine that blocks a protein called BCL-2. This protein is present in some cancer cells. Blocking it can help kill cancer cells.

The brand name for venetoclax is Venclyxto.

Azacitidine

Azacitidine is a chemotherapy medicine that can turn on genes that have been turned off. This includes cancer-suppressing genes that are often turned off in AML cells. Azacitidine can also stop AML cells making proteins, which can stop cancer cells growing and dividing.

Brand names for azacitidine injections include:

• Azacitidine betapharm
• Azacitidine Sandoz
• Azacitidine Seacross
• Azacitidine Tillomed
• Vidaza

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Before starting venetoclax + azacitidine, your haematology team will carry out checks to make sure it is suitable for you. These might include:

• Blood tests to measure your blood counts
  • If your white blood cell count is too high, you might have treatment to lower it before starting venetoclax + azacitidine
• Blood tests to check your liver and kidney function, and the levels of salts in your body
• Bone marrow test

Things to tell your haematology team

Before starting treatment, you should let your haematology team know if you:

• Have kidney disease or liver disease
• Have ever had a heart attack or heart condition
• Have a history of lung disease
• Have an infection, or have had a long-lasting or repeated infection

Some medicines or drugs may interact with venetoclax. It is important to tell your haematology team about any medicines or supplements you are taking. This includes prescribed medicines and medicines you have bought yourself without a prescription. Examples include:

• Herbal medicines, such as St John’s Wort
• Some antibiotic, antifungal and antiviral medicines
• Some medicines used to treat epilepsy
• Some medicines used to treat high blood pressure (including high blood pressure in your lungs)
• Modafinil, a medicine used to treat sleeping disorders
• Digoxin, a medicine used to treat heart failure or abnormal heart rhythms
• Dabigatran, a medicine used to treat and prevent blood clots and stroke

You will receive treatment in a cycle of 28 days. This is made up of some days where you will have venetoclax + azacitidine, and some days where you only have venetoclax.

Dose

Your haematology team will let you know what dose you are on, but below are the most common doses that are used.

Venetoclax

You start on a low dose of venetoclax. Your doctor usually increases the dose every day for 3 days until you reach the full dose. Most people have:

• Day 1: 100mg once a day
• Day 2: 200mg once a day
• Day 3 onwards: 400mg once a day

Azacitidine

Your doctor will work out the best dose of azacitidine for you based on your height, weight and how well you respond to treatment. They will tell you what dose they recommend for you.

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There are several precautions to be aware of when you are taking venetoclax + azacitidine.

• Do not eat, drink or use supplements that contain – grapefruit, Seville oranges (usually used in marmalade) or starfruit. This is because they can increase the amount of venetoclax in your blood.
• Azacitidine injections may make you feel tired or weak or make it difficult to concentrate. Take care if you are driving or using tools or machinery.
• Azacitidine can affect how well your kidneys work. If you stop peeing, or you’re peeing less than usual, tell your doctor straight away.
• Tell your haematology team if you are due to have any vaccines.

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Venetoclax + azacitidine may harm unborn babies.

• If you could get pregnant, it is important to use effective contraception. You need to do this while you are having venetoclax + azacitidine and for 6 months after you stop. The treatment might affect hormonal contraceptive pills or devices. So it is important to use a barrier method like a condom, diaphragm or cap.
• If you could make someone pregnant, it is important to use effective contraception. You need to do this while you are having venetoclax + azacitidine and for at least 3 months after you stop.
• If you think you might be pregnant, tell your haematology team as soon as possible. They may recommend stopping venetoclax + azacitidine for a while. They could also recommend switching to a different treatment.
• If you are planning to get pregnant, or make someone pregnant, tell your haematology team. They can discuss your treatment options with you.

Breastfeeding

Scientists are not sure if venetoclax + azacitidine passes into breast milk. If it does, it could be a risk for breastfed babies or children. You should not breastfeed when taking venetoclax + azacitidine.

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During your treatment with venetoclax + azacitidine you will have regular blood tests. These are usually:

• Before you start treatment
• After each new dose of venetoclax when your dose is being gradually increased
• After reaching your full dose of venetoclax
• Before starting each cycle of treatment with azacitidine

You may also have further blood and bone marrow tests during your treatment. Your haematology team will let you know what tests you need and how often.

Your haematology team will use the results of these tests to:

• Check how well venetoclax + azacitidine is working for you
• Make sure your blood counts have not dropped too low
• Check how well your liver and kidneys are working
• Check the level of salts in your blood

Tumour lysis syndrome

Venetoclax + azacitidine kills cancer cells. When lots of cancer cells breakdown quickly, they can release a large amount of chemicals into your blood. This is known as tumour lysis syndrome. It can affect how well your kidneys work, as well as causing changes to your heartbeat and sometimes fits (seizures). It happens to around 1 in every 100 people having venetoclax + azacitidine. This means 99 in every 100 do not get it.

If you have a very high leukaemia cell count before treatment, your haematology team may consider admitting you for the first week of treatment and might give you medicine to help prevent tumour lysis syndrome. Making sure you stay well hydrated and drinking plenty of water with your tablets can also help prevent tumour lysis syndrome. Your team will monitor you closely so they can treat it quickly if it happens. They may pause treatment for a while or adjust your dose.

Differentiation syndrome

Very rarely, azacitidine injections might cause a serious problem called differentiation syndrome. This can happen if recovering white blood cells release too many immune chemicals, which can trigger a severe reaction.

Your haematology team will monitor you for signs of differentiation syndrome. If it happens, it can be treated with steroids.

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You usually carry on having venetoclax + azacitidine unless:

• It has not worked well enough
• It stops working well
• You are having side effects that are difficult to cope with

If this happens, your haematology team might stop venetoclax + azacitidine, adjust your dose or recommend a different treatment.

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You may get some side effects while you are taking venetoclax + azacitidine. Some people may have very few side effects, whereas other people experience more serious side effects.

Tell your haematology team about any side effects you have. They may be able to suggest things you can do or give you medicines to help.

If you are getting side effects that are difficult to cope with, your haematology team might suggest:

• Temporarily stopping treatment
• Lowering your dose of venetoclax + azacitidine
• Delaying your next azacitidine treatment cycle

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The most common serious side effects for people having venetoclax + azacitidine include:

• A high temperature (higher than 38°C) with a low white blood cell count (febrile neutropenia). You might also feel shivery or generally unwell.
• Pneumonia (a lung infection). You may get symptoms like:
  • A cough, chest pain, shortness of breath, wheezing.
  • A high temperature.
  • An aching body, feeling very tired, loss of appetite.
• Sepsis, which is a life-threatening reaction to an infection. You may get symptoms like:
  • Feeling confused, slurring your words, not making sense.
  • Blue, grey, pale or blotchy skin, lips or tongue. This may look different on black or brown skin.
  • A rash that doesn’t fade when you roll a glass over it.
  • Difficulty breathing, shortness of breath or breathing very fast.

Most common side effects affect more than 20 in every 100 people who are having venetoclax + azacitidine. Most common side effects include:

• A low platelet count, which might lead to unexpected bruising or bleeding like nosebleeds, bleeding gums, blood spots or rashes
• A low white blood cell count, which might mean that you get infections more often and any infections you get might last longer than usual
• A low red blood cell count (anaemia), which can make you feel tired, dizzy or short of breath
• Low potassium levels which can cause muscle weakness, muscle cramps and a fast and irregular heartbeat
• A build up of fluid, in your legs, ankles and feet and sometimes your arms and hands
• An irregular, pounding, fluttering or fast heartbeat
• Fever
• Fatigue
• Decreased appetite
• Feeling sick or being sick
• Diarrhoea
• Constipation

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If venetoclax + azacitidine are not working well, your haematology team might suggest altering your treatment cycle, your dose, or stopping treatment if your blood counts drop.

If this is not suitable for you, or does not work, they will talk to you about your treatment options.

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