CAR T-cell therapy

CAR T-cell therapy is a type of immunotherapy. You might also hear it called a type of adoptive cell transfer.

CAR T-cell therapy is a very complex and specialist treatment. With this treatment, a specialist collects and makes a small change to your T cells. After a few weeks, you have a drip containing these cells back into your bloodstream. The CAR T-cells then recognise and attack the cancer cells. 

It is available as a possible treatment for some children with leukaemia and some adults with lymphoma. People with other types of cancer might have it as part of a clinical trial. 

T cells

To understand CAR T-cell therapy more, it helps to understand what T cells do.

White blood cells called lymphocytes play an important part in fighting infection and diseases, including cancer. There are different types of lymphocytes. T cells are one type.

T cells move around the body to find and destroy defective cells. When you come into contact with a new infection or disease, the body makes T cells to fight that specific infection or disease. It then keeps some in reserve so that if you come across the infection again your body can recognise it and attack it immediately. 

What is CAR T-cell therapy?

T cells are good at fighting infection. But it can be difficult for them to tell the difference between a cancer cell and a normal cell. So the cancer cells can hide away and not be recognised.

Scientists are trying to find ways to get T cells to recognise cancer cells. One possible way to do this might be CAR T-cell therapy. 

How does it work?

Your medical team take a sample of T cells from your blood. This process is called apheresis.

In the lab, they change the T cells. You might hear this called genetically engineering the T cell. The T cell is now a CAR T-cell. CAR stands for chimeric antigen receptor. These CAR T-cells are designed to recognise and target a specific protein on the cancer cells.

These changed T cells grow and multiply in the lab. Once there are enough cells you have a drip containing these cells back into your bloodstream. The aim is for the CAR T-cells to then recognise and attack the cancer cells.

The changes they make in the lab mean that they can stay in your body for long periods of time, recognising and attacking the specific cancer cells. Researchers are still looking into how long they might stay in the body.

There are different types of CAR T-cell therapy made by different companies. Examples include:

• tisagenlecleucel (Kymriah) 
• axicabtagene ciloleucel (Yescarta)
• brexucabtagene autoleucel (Tecartus)

Who can have CAR T-cell therapy?

CAR T-cell therapy is available for some children with leukaemia and some adults with lymphoma.

This followed decisions by the National Institute for Health and Care Excellence (NICE) in England in December 2018 and January 2019. And decisions by the Scottish Medicines Consortium (SMC) in 2019.

Healthcare in Wales and Northern Ireland generally follow NICE guidelines. The following is a summary:

Children and young people

CAR T-cell is recommended for those up to the age of 25 who have a type of leukaemia called B cell ALL. It will be used in one of the following situations:

• newly diagnosed children or young people whose leukaemia hasn’t gone away with 2 cycles of treatment
• their disease has come back (relapsed) following a stem cell or bone marrow transplant
• their disease has relapsed twice or more
• children and young people whose leukaemia had gone away with treatment, but it’s come back, and chemotherapy isn’t working now
• their disease has come back once but they can’t have a stem cell transplant because either they aren’t well enough, or they don’t have a donor

Adults

For adults, it will also be available for some people with one of the following types of lymphoma:

• diffuse large B cell lymphoma
• primary mediastinal B cell lymphoma
• mantle cell lymphoma

It is for those adults whose: 

• diffuse B cell lymphoma or primary mediastinal lymphoma has continued to grow or relapsed following at least 2 treatments
• mantle cell lymphoma has continued to grow or relapsed following treatment with a type of targeted drug called a Bruton’s tyrosine kinase inhibitor (eg ibrutinib)

So this treatment is only suitable for a small number of children and young people, and around 200 adults each year. It is not used as a treatment outside of clinical trials for other types of cancer in children or adults.

Information about centres in the UK

England

Only a small number of centres in England can provide this specialist treatment. There are 8 centres for adults and 9 centres for children and young people. 

Wales and Northern Ireland

Wales has one centre that offers this treatment. Some patients from Wales will have treatment here. And some other patients will travel to hospitals in England to have CAR T-cell treatment. 

Scotland

There is one centre for adults in Scotland providing CAR T-cell treatment. Children will travel to England for treatment.

Having CAR T-cell therapy

Collecting your T cells

First you have a tube (cannula) put into a vein in each arm. You might need a special tube called a vascath if your veins in your arms aren’t big enough for the cannula.

One tube removes the blood and passes it into an apheresis machine. The machine separates the different parts of the blood.

For CAR T-cell therapy, the machine takes out your T cells. The rest of your blood cells and normal blood fluid go back into your body through the tube in your other arm.

It can take 4 to 5 hours to collect your T cells.

The doctors send your T cells to the laboratory to make CAR T-cells. This can take several weeks. When they have enough CAR T-cells, they freeze them.

Chemotherapy

You have chemotherapy before you have CAR T-cell therapy. This lowers your number of T cells and prepares your body for the CAR T-cells. Doctors call this lymphodepletion. You have the chemotherapy over a few days before you have the CAR T-cell infusion.

Having the CAR T-cells

The specialist nurse defrosts the CAR T-cells on the ward. They give you medicines into your vein to stop allergic reactions. They then give you back the cells as a drip into your bloodstream. This usually takes less than 30 minutes. The doctors and nurses monitor you closely during and after the treatment. 

Staying in hospital

The doctors and nurses need to monitor you closely for 2 weeks after CAR T-cell therapy.

You either stay in hospital. Or you stay in a hotel or other residence nearby, which the hospital pays for. You then go to the day care unit every day. This is called an ambulatory clinic or Ambi-care and is only available at some hospitals. You will have to stay in hospital if you develop complications.

Your healthcare team usually recommend that you are within an hour’s drive of the treatment centre for up to 28 days after the treatment.

Side effects

This is a new treatment, so doctors might not know about all the possible side effects yet. Known side effects include:

• allergic reaction
• cytokine-release syndrome
• changes in the brain (neurological side effects)
• increased risk of infection
• high uric acid levels in the blood, due to cancer cells breaking down quickly (tumour lysis)

Allergic reaction

You might have an allergic reaction to the CAR T-cells. Symptoms of an allergic reaction include high temperature (fever), chills, feeling or being sick and difficulty breathing. 

Your nurse will give you medicines beforehand to try to prevent a reaction. Tell your nurse straight away if you have any symptoms of an allergic reaction. They will monitor you closely during and after the treatment.

Cytokine release syndrome

Cytokines are group of proteins in the body that play an important part in boosting the immune system. CAR T-cell therapy stimulates the immune system to make large amounts of cytokines. It causes symptoms such as:

• fever (high temperature)
• dizziness due to low blood pressure
• difficulty breathing

This syndrome might happen in the first couple of weeks after treatment. You can have treatment to reverse the syndrome.

Your doctors and nurses monitor you closely. If you develop any signs of this syndrome, they assess how severe they are. You might need treatment with a monoclonal antibody called tocilizumab to control cytokine release syndrome. Some people need to go to the Intensive Care Unit (ICU).

Side effects affecting the brain (neurological side effects)

Sometimes CAR T-cells cause problems to the brain. Doctors call this neurotoxicity. Symptoms can range from being mild to severe and might include:

• headaches
• altered consciousness
• becoming confused or disorientated
• speech changes
• seizures

The treating team monitors you, or your child, closely for any of these changes. The changes might go away on their own or you might need treatment, for example steroids. Treatment depends on the symptoms you, or your child, are experiencing and how serious they are.

Increased risk of infection

Some types of CAR T-cell therapy can increase your risk of infection.

In treatment for some leukemias and lymphomas, CAR T-cells are designed to recognise a protein called CD 19. CD 19 is found on the surface of most B cells. B cells are a type of white blood cell and, like T cells, they play an important part in fighting infection. 

CAR T-cell therapy that targets the CD 19 protein also destroys the B cells. It kills normal B cells as well as cancerous B cells. This either reduces the number of B cells or destroys them all. This makes it difficult for you to fight infections. 

You might need treatment for this side effect. This treatment is called immunoglobulin therapy. It contains antibodies to help you fight infection.

High uric acid levels in the blood, due to cancer cells breaking down quickly (tumour lysis)

This can happen when CAR T-cell therapy breaks down lots of cancer cells quickly. As the cancer cells break down, they release a chemical called uric acid into the blood. It’s hard for the kidneys to cope with the high levels of uric acid.

You have regular blood tests to check for this. If you develop tumour lysis syndrome you have fluids into your vein and medicine to help lower the levels of uric acid in your blood.

Cancer Research UK Science blog

To read more about the science behind this treatment read the science blogs.