CAR T-cell therapy

CAR T-cell therapy uses blood cells called T cells.

• T cells are a type of white blood cell. They are also called T lymphocytes.
• They are part of your immune system, which helps your body fight infections.
• T cells usually recognise and destroy damaged or infected cells. This includes cancer cells.
• But cancer cells are good at disguising themselves so your T cells can’t spot them.
• CAR T-cell therapy is a way of training your T cells to recognise cancer cells they could not find before.

CAR stands for chimeric antigen receptor. It’s a technical name based on the way the T cells are modified.

In the UK, three different CAR T-cell therapies are approved to treat ALL. They all work in a similar way.

Brexucabtagene autoleucel (brexu-cel)

• Brand name Tecartus
• Suitable for people 26 and over
• Available to treat B-cell ALL that has not responded or has come back after treatment

Obecabtagene autoleucel (obe-cel)

• Brand name Aucatzyl
• Suitable for people 26 and over
• Available to treat B-cell ALL that has not responded or has come back after treatment

Tisagenlecleucel (tisa-cel)

• Brand name Kymriah
• Suitable for people 25 and under

Available to treat B-cell ALL that has not responded to treatment, has come back after a stem cell transplant or has come back more than once

Scientists do not know if CAR T-cell therapy itself affects fertility. But some of the medicines used to prepare you for the treatment may affect your fertility.

If you might want children in the future and you have not already discussed your fertility, tell your doctor or nurse. They can talk to you about your options. This could include freezing eggs, sperm or embryos. This may not be possible for everyone. Your haematology team may refer you to a fertility specialist.

Scientists do not know if CAR T cells are passed on to a baby during pregnancy. If they are, they could potentially harm your baby.

• If you could get pregnant, you will have a pregnancy test before starting treatment.
• If you are pregnant, your team will talk to you about the risks and benefits of treatment.

CAR T-cell therapy is not recommended for pregnant women.

If you could get pregnant, you must use effective contraception during CAR T-cell treatment and for some time afterwards. Your team will tell you how long this needs to continue. It must include at least one barrier method, like a condom, diaphragm or cap.

Scientists do not know if CAR T cells pass into breastmilk. If they do, they could potentially harm your baby.

Your CAR T team should talk to you about psychological support you might need during and after your treatment. Some centres may offer counselling or an appointment with a psychologist. Others might signpost you to charities or other support organisations that can help.

We offer a counselling service that can help you, and your family members, access up to six sessions of counselling, free of charge.

Your CAR T team may be able to recommend other support services for you and your caregiver.

You’ll have lots of tests and scans to make sure CAR T-cell therapy is suitable for you. And that you are well enough to have it. These might be at your local hospital or at your CAR T centre.

These might include:

• Blood tests to check your blood counts, liver function and kidney function
• Blood tests to check for viral infections that could flare up
• Tests and scans to check your heart and lung function
• A pregnancy test
• Dental checks
• A lumbar puncture or brain scan, if you have ALL in your central nervous system

You might not need all these tests. Depending on your symptoms and results, you might have other tests too.

Your nurse will ask for a sample of your handwriting so they know what it usually looks like. Every day during your recovery, they’ll ask you to write the same sentence and compare it to your usual handwriting. This helps them check for complications.

CAR T-cell therapy involves having lots of medicines through a drip. You’ll also have frequent blood tests. Your team may fit a central line to make this easier, if you don’t already have one.

You might not start CAR T-cell therapy straight away. In this case, you may need treatment to keep your ALL under control until you have your T cells collected. This is called holding treatment.

If you need it, your team will tell you what holding treatment they recommend for you.

If you have children, you may need to arrange for someone to look after them. You might have family or friends who can help. Your child’s school may offer breakfast or after-school clubs. Or you may consider contacting your council’s family information service.

Macmillan have more information about arranging childcare.

You might need to arrange for someone to look after your home while you’re away. This might include looking after pets or watering any plants you have.

For the first 28 days after having CAR T cells, you must stay within 1 hour’s travel from your CAR T centre. You must have an adult with you at all times.

• The exact distance varies depending on your treatment and your hospital’s policy. Some centres might let you stay further away. It is important to follow your centre’s recommendation.
• If you live further away, you’ll need accommodation close to the hospital. Your CAR T team should be able to help arrange this free of charge.

Our CAR T away from home service can help with costs or accommodation if you need it.

If you leave hospital less than 28 days after having your CAR T cells, you’ll need an adult to stay with you all the time. They must be able to drive so they can take you back to hospital quickly if they need to.

They’ll also help monitor your symptoms to help spot any complications early. Your CAR T team will explain what they need to do, what symptoms to record and when to seek help. They should also discuss what support is available, as it can be difficult emotionally.

You’ll need to consider who might be able to do this for you. If you do not have an adult who’s able to support you, you may need to stay in hospital for these 28 days.

Ask your team about the facilities on the ward you’ll be staying on, like a fridge, TV or wifi.

There are some essentials you’ll need for your hospital stay. Things to keep you occupied are also a good idea, as you might spend a lot of time on your own. You may also want things to help make your stay more comfortable.

We have separate suggestions to pack for a hospital stay.

You’ll need some time off work, school or education during your treatment and recovery. Speak to your CAR T team about what they expect for you.

You may want to talk to someone about your needs and adjustments. This could be your manager, HR, occupational health, workplace union, teacher or student union. When talking to them, you might want to:

• Explain that you’re having treatment and will need time off
• Find out what support or adjustments they can offer
• • Ask about sick leave, sick pay, occupational health or other policies

Our advocacy and welfare team are here if you need advice on finances, help applying for benefits, or support with employment issues.

Your CAR T team may recommend other organisations who can support you.

You usually go to your CAR T centre to have your T cells collected. Unless you’re already staying in hospital, you can usually go home afterwards.

Steroids and some other medicines affect the number of T cells in your blood. You’ll need to stop these a few days or weeks before having your T cells collected. Your team will tell you what medicines you should stop and when to stop them. You might need other approaches to help relieve your symptoms during this time.

It usually takes 3 to 6 hours to collect your T cells, so it’s a good idea to take something to do. You’ll have to keep fairly still so you won’t be able to walk around.

• You’ll have blood tests first to check your blood counts, liver and kidney function, mineral levels, and test for infections.
• A doctor or nurse will measure your height and weight. This helps them work out how much blood they need to take from you.
• They put a thin plastic tube in each of your arms. If you already have a central line, they’ll check if it’s suitable to use this instead.
• They connect the tubes to a machine.
• The machine takes blood out of one arm. The blood passes into the machine, which filters out your T cells. The rest of your blood goes back into your other arm.
• It takes about 3 to 6 hours. A nurse checks your heart rate, temperature and blood pressure throughout.
• When it’s done, the T cells are sent to a lab. Depending on which T cell therapy you are having, they might be frozen first.

The process uses an additive to stop your blood clotting. This can sometimes cause low calcium levels.

Tell your team if:

• You feel numbness or tingling around your mouth or in your hands or feet
• You get muscle cramps
• You are feeling sick or being sick

They can give you calcium supplements if you need them.

Your T cells are sent away to a lab, which might be in the UK or overseas. Here, scientists modify the cells so they can recognise and stick to proteins on the surface of your leukaemia cells.

After the scientists have modified your cells, they grow them so there are enough for your treatment. Then they freeze them and send them back to your hospital.

Sometimes, the manufacturing process doesn’t work as expected. It might not be possible to make the CAR T cells, or there might not be enough of them. If this happens, your haematology team will discuss your options with you.

Making the CAR T cells can take a few weeks. You’ll probably need treatment to keep your leukaemia cell count as low as possible while you wait. This is called bridging therapy. You might have it at your usual hospital or at your CAR T centre.

Your team will explain what bridging therapy they recommend for you. It could be:

• Chemotherapy
• A targeted medicine like imatinib
• An antibody treatment like inotuzumab ozogamicin

You might have a bone marrow test during this time too.

After your CAR T cells have arrived back from the lab, you have a short course of chemotherapy. This reduces the number of white blood cells and immune chemicals in your bloodstream. It makes your body less likely to react to the CAR T cells and helps them work better.

You might hear people call it lymphodepleting therapy or conditioning therapy.

You have conditioning therapy about a week before having your CAR T cells.

• Most people stay at their CAR T centre to have it. But some people might have it at their usual hospital.
• Most people have a combination of chemotherapy medicines called fludarabine and cyclophosphamide.
• You have them over a few days, with a gap of at least 2 days before having your CAR T cells.

Conditioning chemotherapy can cause very low blood cell counts for a few weeks. So you’ll probably have medicines to help prevent infections too. You’ll also have medicines to help prevent a complication called tumour lysis syndrome.

The day you have your CAR T cells is sometimes called day 0. It only takes a few minutes. Some people say it feels like an anti-climax.

On the day:

• A specialist nurse checks you are well enough to have the CAR T cells. They explain what will happen and ask for your consent.
• The nurse gives you paracetamol and antihistamine. This reduces the risk of having a reaction to the CAR T cells.
• If you do not have a central line, they put a thin plastic tube into your arm. If you have a central line, they can use this instead.
• The nurse defrosts the CAR T cells and gives them to you straight away through a drip into your arm or central line. It only takes a few minutes.
• They stay with you all the time to check for any reactions to the cells.
• Once you’ve had the cells, the nurse gives you fluids through the drip. This makes sure there are no cells left in the drip tubing.

Some people have a mild reaction to the preservative used to store the CAR T cells. Tell your team straight away if you:

• Feel warm or flushed
• Get a rash
• Start coughing

You or your visitors might notice a smell a bit like boiled sweetcorn. This is from a preservative added to the CAR T cells so they’re not damaged by the freezing process. It’s harmless. Your body gets rid of it in your pee, sweat and breath. The smell might last for a couple of days.

If you are having obe-cel (Aucatzyl), you have a second dose of CAR T cells 9 days later. The 28-day monitoring period is counted from the first dose.

Most people who have CAR T-cell therapy have very low levels of healthy B cells, or sometimes no B cells at all, for at least 6 months after treatment. For some people it can last much longer. You might hear your team call this B-cell aplasia.

B cells usually make antibodies, which help your body fight infections. If you have low B cells, you have a higher risk of getting infections.

• You will have blood tests to monitor your B cell counts. You may need to have these for the rest of your life.
• You will also have blood tests to measure your antibody levels.
• If your antibody levels are low and you get repeated or long-lasting infections, you might need immunoglobulin replacement therapy. This tops up your antibody levels. You have it through a drip or as an injection under your skin.

CAR T-cell therapy can cause low levels of white blood cells called neutrophils. This is called neutropenia.

After CAR T-cell therapy, neutrophil counts typically start to improve but then have a second drop.

• When your neutrophil count is low, you will need to take precautions to reduce your risk of infection.
• You might need growth factor treatment to help boost your white blood cell counts. You have it through a drip or as an injection under your skin. You might hear your team call it GCSF.

• A high temperature (38°C or higher)
• Flu-like symptoms
• Fatigue or lack of energy
• Headache
• Tremor
• Changes in your heart rate
• Feeling confused or agitated
• Changes to your handwriting
• Difficulty speaking or finding words
• Sore throat, sneezing, blocked or runny nose, earache
• Coughing or shortness of breath
• Burning or stinging when you pee, or peeing more often than usual
• Sickness or diarrhoea
• Pain, redness or swelling around your central line

After CAR T-cell therapy, you might not respond as well to vaccines as other people. But they still offer you some protection against infection.

• You can have flu or covid vaccines from 3 months after CAR T-cell therapy. Some centres wait longer than this.
• You can have other non-live vaccines from 6 months after CAR T-cell therapy, as long as you have not had immunoglobulin replacement therapy in the past 2 months.
• You should not have live vaccines for at least 1 year after CAR T-cell therapy, or until your immune system has recovered.

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