What is CAR-T cell Therapy?

In order to determine if you are eligible for CAR-T cell therapy you will need to be reviewed by one of our doctors in the Alfred CAR-T clinic. Your cancer type, previous treatments, and other medical conditions will be assessed and you will be physically examined to make sure you are healthy enough to receive treatment. You will also be assessed by a Neurologist to help us monitor for any neurological changes after you receive CAR-T therapy. You may need some additional investigations including blood tests, body scans, and a bone marrow biopsy. Your case will also need to be discussed at one of our CAR-T multidisciplinary team meetings before approval can be given for CAR-T cell therapy.

In order to re-engineer your T cells, we need to first collect them from your body, this happens through a procedure called leukapharesis. Leukapheresis removes some of the white cells in your blood through a needle inserted into the arm and connected to a leukapharesis machine. Blood is taken from one arm, processed in a cell separator to remove the white blood cells, and the remaining blood components are returned to you through the other arm. You will receive a blood thinner (anticoagulant solution) which will allow us to collect your white blood cells without them sticking together. Before this procedure, the veins in your arm will be assessed by a nurse to determine if the procedure will be successful. Sometimes, a larger needle called a vascath will need to be inserted by a doctor. During the leukapheresis procedure, the total volume of blood circulating through your body will pass through the leukapheresis machine 1-2 times. The process can take up to 4 hours. There is a very small risk that we will not be able to collect enough cells to make your dose of CAR-T cells. If this is the case, your study doctor will discuss with you the possibilities of using fewer T cells or undergoing a second leukapheresis procedure.

Once your T cells are collected, they will be sent to a manufacturing laboratory. Sometimes you T cells will be frozen (cryopreserved) to keep them healthy during this process. At the laboratory, genetic material is inserted into your cells using a virus. The virus has been changed in the laboratory so that it is not likely to reproduce or cause an infection once it is in your body. The final CAR-T cell product is also tested for any infections to make sure it is safe to give back to you. The process of transporting and manufacturing your T cells can take several weeks. If your cancer needs treatment before your CAR-T cells are ready, you may need a short course of chemotherapy before you receive your CAR-T cells (‘bridging therapy’). Sometimes, your T cells cannot be successfully re-engineered, or may become lost or damaged during manufacture. In this case, your T cells may need to be collected again.

Once your CAR-T cells have been returned from the manufacturing laboratory, you will be booked for admission to hospital to receive conditioning chemotherapy to prepare your immune system for CAR-T cells. This therapy involves two drugs called fludarabine and cyclosphosphamide that are given through an intravenous drip over a few days in hospital. Chemotherapy may cause a number of side effects including allergic reaction, nausea or vomiting, diarrhoea, mouth ulcers, hair loss, injury to you kidneys, liver, lungs or heart, and a fall in your blood cells (red blood cells, white blood cells, and platelets) that can make you feel tired or short of breath, and put you at risk of infections or bleeding. You will be closely monitored for any of these complications whilst in hospital and may require blood transfusions or medications to treat or prevent any side effects.

Following conditioning chemotherapy, your CAR-T cells will be given back to you through an intravenous drip. This infusion usually takes less than 30 minutes, during which time you will be closely monitored for any reactions to the cells or the liquid they are preserved in. You will be given medications before the infusion to lessen your chances of having a reaction. After your CAR-T cell infusion, you will need to remain in hospital for 10 to 14 days to monitor for and treat any side effects.

The most common side effect from CAR-T cell therapy is Cytokine Release Syndrome, an inflammatory reaction caused by the CAR-T cells growing in your body and attacking your cancer cells that can cause fevers, chills, body aches, shortness of breath, or low blood pressure. Sometimes this inflammatory reaction can also affect the brain (Neurological toxicity) leading to drowsiness, confusion, changes in personality, difficulty writing, speaking or moving, and even seizures or coma. Medications will be given to you if you experience these symptoms and you may need to be admitted the intensive care unit for breathing or blood pressure support. Other possible side effects from CAR-T therapy and conditioning chemotherapy include the breakdown of cancer cells which may damage your kidneys (Tumour Lysis Syndrome), damage to other organs, an increased risk of infection, persisting low blood cell counts, changes to your fertility, and an increased risk of other types of cancer later in life.

After you leave the hospital you will be closely monitored as an outpatient until at least one month after CAR-T infusion to allow our team to quickly manage any side effects that may develop. During this time you must be supervised by a full time carer (a family member, partner or friend) and must stay within two hours drive of the hospital. We can assist you with accommodation if you have nowhere else to stay. You will also not be able to drive for the first 8 weeks following CAR-T infusion. If you are well after your first 28 days, you will be allowed to return to your normal residence and will continue to be followed up in the CAR-T clinic or over the phone at regular intervals.