CAR T-cell therapy

You will need a number of tests to make sure you are ready for your CAR T-cell treatment.

These may include:

• Electrocardiogram (ECG) and echocardiogram (echo) to check that your heart is healthy.
• Blood tests to check your full blood count (the levels of blood cells in your blood), and how your liver and kidneys are working. We will also test your blood for viruses, including HIV, Hepatitis B and C, HTLV 1 and 2, and other infections such as syphilis and toxoplasmosis.
• CT/MRI/PET scans to find out how well your disease has responded to the latest treatment.
• Lung function test, to check how well your lungs are working.
• Creatinine clearance or glomerular filtration rate (GFR) scan, to check your kidney function.
• Bone marrow biopsy (taking a sample of your bone marrow) to check if your bone marrow has been affected by your disease.

Your doctor, clinical nurse specialist (CNS) or the trials research nurse will talk to you about the tests you need in detail. Information about these tests is available separately. If you’d like more information, please ask the team looking after you.

Leukapheresis is a way of collecting and separating your T-cells from the other blood cells using a machine called a ‘cell separator’. There are two ways we can collect your T-cells using the cell separator:

1. Via a catheter (a thin semi-rigid tube) called a vascath inserted into a large vein at the top of your leg. Before we insert the vascath, we will apply local anaesthetic to your skin to numb it. This means that you will be awake for the insertion but you will not feel any pain. Once inserted, we will connect the vascath to the cell separator. During leukapheresis, blood will be taken from the vein into the cell separator, which will separate the T-cells from the other blood cells and collect them into a collection bag. The rest of the blood will be returned to you via the same vein. After the collection finishes, we will remove the vascath and put a dressing on the wound. We will also monitor you for any side effects, such as bleeding.
    
2. Via a cannula (a small plastic tube) inserted into a vein in each arm. Each cannula will then be connected to the cell separator. During leukapheresis, blood will be taken from one arm into the cell separator, which will separate the T-cells from the other blood cells and collect them into a collection bag. The rest of the blood will be returned to you via the other arm.

Leukapheresis is performed by expert nursing staff in the University College Hospital Macmillan Cancer Centre. It takes around six hours to complete. This includes any checks before and after the procedure, and a blood test before you leave the Cancer Centre.

Leukapheresis is well tolerated, with very few side effects. The nurse carrying out the procedure will monitor you closely.

In most patients, leukapheresis collects enough T-cells to initiate CAR T-cell production. If we don’t collect enough T-cells, this may be due to extensive chemotherapy you had before. Your doctor will talk to you about alternative options if this happens.

Your doctor, CNS or the trials research nurse will explain the procedure to you in detail and ask you to sign a consent form. This will confirm that you agree to go ahead with leukapheresis and understand what it involves. You can also find a more detailed information sheet about leukapheresis in your CAR T-cell pack.

When the leukapheresis is complete, your cells will be taken to a CAR T-cell manufacturing laboratory by a courier. There, a new gene is introduced into your T-cells, converting them into CAR T-cells. This enables them to recognise and kill cancer cells.

The CAR T-cell manufacturing process takes at least four to six weeks. Once completed, we will arrange a date for your CAR T-cells to be sent back to us. At that point we will also contact you to arrange admission for your CAR T-cell therapy.

In a small number of people, CAR T-cell manufacture may not be successful. If this happens, your doctor will talk to you about alternative options. ‘Bridging’ therapy is the name given to treatment that you receive between the leukapheresis and the admission for CAR T-cells. In some patients, the disease needs to be ‘kept under control’ for the four to six weeks while the CAR T-cells are being produced. We will arrange this with your referring hospital and talk to you about this during your clinic appointment at UCLH.

Before you can have the infusion of the CAR T-cells, you will need to receive several days of ‘conditioning’ chemotherapy. This takes place in the UCLH Ambulatory Care Unit or on one of the haematology inpatient wards. Conditioning chemotherapy prepares your immune system to receive the CAR T-cells. 

It does this by reducing the number of normal T-cells in the blood and creating space for the modified cells to grow. The type and duration of chemotherapy will depend on your underlying condition and the CAR T-cells, and so varies for each person. As with any chemotherapy treatment, there are potential side effects. You will receive separate chemotherapy information with more details.

On the day of infusion, a doctor will review you to make sure you are fit to go ahead with the treatment. Once you are ready, your nurse will:

• give you medication into the vein to prevent allergic reactions
• start an infusion of fluids into the vein via a cannula
• check your blood pressure, temperature, oxygen levels and pulse.

Your CAR T-cells will be delivered in a frozen state. Your healthcare team will carry out several identification checks on you and your CAR T-cells, before they are thawed in a water bath. Once thawed, they will be infused into your vein via a cannula. The infusion takes about 10 to 20 minutes. When finished, your nurse will flush the drip with saline.

The CAR T-cells have a preservative added to them so that the freezing process doesn’t damage the cells. The preservative carries a smell similar to sweetcorn. You may not be able to detect the smell, but your family and visitors may notice it for around 24 hours following the infusion.

Please note: If you are receiving CAR T-cell therapy as part of a clinical trial, the guidance below may be different for you. Your clinical trials team will advise you.

After your CAR T-cell infusion you will remain on the inpatient ward for at least 14 days, where you will be monitored for any side effects. More information about the side effects is included below.

Your doctor will advise you when it is safe for you to leave hospital. After the initial minimum 14 days, you may either be able to move to the Ambulatory Care Unit or go home. To be able to go home, you will need to remain within one hour's travel distance of UCLH for a further 14 days.

Whether you are at home or in the Ambulatory Care Unit, a next of kin or carer will need to stay with you at all times until the 28-day period has passed. This is so that they can support you during your recovery and look out for signs of infection or neurological problems.

Please note that some patients may need to stay in hospital or Ambulatory Care longer than 28 days. We want to make sure that you are fit and well before we discharge you so that you have a better recovery at home.

You will have several follow-up appointments to assess your recovery and response to treatment. If you need further tests or scans, we will discuss them with you at your follow-up appointment.

Please follow the advice below and on the next page to help with your recovery:

• Call your CAR T-cell team immediately if your temperature is 38°C or higher, or if you feel unwell for any other reason.
• Drink two to three litres of fluid a day unless you have been advised otherwise.
• Wash your hands with warm water and soap regularly, especially after using the bathroom and when preparing food.
• Cook meat and eggs all the way through to kill any germs.
• Carefully wash raw fruits and vegetables.
• Avoid gardening and crowded areas as both increase your risk of infection.
• Brush your teeth after every meal.
• Avoid driving or operating heavy machinery for two months after the infusion.
• It may be helpful to have someone live with you for several weeks after you leave hospital. They can help with day-to-day activities while you are recovering and look out for symptoms of infection or neurotoxicity (please see page 5 for more information).
• Keep your contact card and your irradiated blood card with you at all times.
• Whenever you contact any health professional to discuss your symptoms, let them know that you have recently received CAR T-cell therapy.

CAR T-cell therapy can cause some serious side effects. It is important that you and your family or carer understand what to look out for, and notify your hospital team if any of these side effects occur.

Allergic reactions

The infusion of the CAR T-cells may cause allergic reactions such as fever (temperature above 38°C), shivers, difficulty breathing, low blood pressure, rash or vomiting. The CAR T-cell team will monitor you closely during and after the infusion for any of these symptoms.

Cytokine release syndrome (CRS)

The CAR T-cells may stimulate the release of chemicals into your bloodstream called cytokines. These can cause severe reactions, referred to as ‘cytokine release syndrome’ (CRS). Symptoms of CRS include fever, fatigue, shortness of breath, decreased urine production, nausea and vomiting, diarrhoea, irregular heartbeat and headache. CRS can be severe, and even life-threatening. For some patients it may also mean a transfer to the Intensive Care Unit. The CAR T-cell team will monitor you closely and, if necessary, give you treatment to control the CRS, such as antibody therapy.

Neurotoxicity

CAR T-cell therapy can sometimes temporarily affect brain function. It can cause mild symptoms such as confusion or drowsiness in some patients, and severe symptoms such as seizures and reduced consciousness in others. Some patients with more severe symptoms may be transferred to the Intensive Care Unit. Where necessary, corticosteroids will be given to treat the syndrome. To identify neurotoxicity early, all patients undergoing CAR T-cell therapy have their brain function assessed daily during their hospital stay. Some patients will also need to take medicine to prevent seizures from the point of being admitted to hospital. Your CAR T-cell team will advise you if this applies to you.

Tumour lysis syndrome (TLS)

CAR T-cell therapy can destroy large amounts of cancer very quickly. This can release high volumes of toxins into the blood that can put a strain on the kidneys, making them less efficient at producing urine. This is TLS. On occasion, TLS can be life-threatening. For this reason, all patients undergoing CAR T-cell therapy have once or twice daily blood tests during their hospital stay. If TLS is identified, you will have fluids via a drip and medication 
to help remove the toxins. Rarely, dialysis may need to be used.

Increased risk of infection

If you have B-cell leukaemia or B-cell lymphoma, you will be at an increased risk of infection. This is because the CAR T-cells cannot discriminate between cancerous B-cells and healthy B-cells so will kill both. As B-cells are responsible for producing antibodies that help to fight infection, low levels of healthy B-cells can lead to an increased infection risk. To help prevent this, we will monitor your immunoglobin levels in the blood and give you replacement antibodies via a drip if needed.

Risk of second cancer

CAR T-cell therapy is created through introduction of a new gene into your normal T-cells. This has the potential to cause T-cells to grow in an uncontrolled way, similar to some blood cancers like leukaemia. This has not been reported yet in patients treated worldwide with CAR T-cell therapy, but remains a theoretical risk. We monitor all patients undergoing CAR T-cell therapy on a long-term basis for symptoms of secondary cancers. You should also follow the same general advice given to all patients receiving chemotherapy and/or radiotherapy, such as avoiding smoking and excessive exposure to UV rays.

Risk to the unborn child

The level of this risk is currently unknown, but women of childbearing age must have a negative pregnancy test before leukapheresis and conditioning chemotherapy to proceed to CAR T-cell therapy. All patients will need to use two forms of contraception from the time they consent to treatment and for 12 months after the infusion. Talk to your doctor, CNS or trials research nurse if you need advice about contraception.

We want to involve you in all the decisions about your care and treatment. The team looking after you will answer any questions you may have so please ask if anything is unclear.

If you decide to go ahead with the CAR T-cell therapy, we will ask you to sign a consent form. This confirms that you agree to have the procedure and understand what it involves.

Macmillan Cancer Support

Tel: 0808 808 00 00        

Website: macmillan.org.uk  

Lymphoma Action

Tel: 0808 808 5555

Website: lymphoma-action.org.uk  

Blood Cancer UK

Tel: 0808 2080 888        

Website: bloodcancer.org.uk  

Leukaemia Care

Tel: 08088 010 444

Website: leukaemiacare.org.uk  

Cancer Research UK

Tel: 0808 800 4040        

Website: cancerresearchuk.org  

Myeloma UK

Tel: 0800 980 3332

Website: myeloma.org.uk  

University College London Hospitals NHS Foundation Trust cannot accept responsibility for information provided by external organisations.

If you have any queries or concerns, please contact your team:

Consultant: ......................................................................................................................

Clinical nurse specialist (CNS): .....................................................................................

Trials practitioner/research nurse: ................................................................................

(You can print out this page and add the names of your clinical team if you wish.)

• In an emergency, call 999 for an ambulance or go to your local hospital.
• For a medical issue out of hours, please call 07852 220 900.
• For non-urgent issues between 9am and 5pm Monday to Friday, please call the CAR T-cell trials team on 020 3447 2528; or the haematology helpline (if you are not a trial patient) on 020 3447 7359.
• Hospital switchboard: 020 3456 7890