CAR-T cell therapy: how it works, who it is for and the risks

What is CAR-T therapy?

T cells are immune cells that can destroy infected or damaged cells, but cancer cells often find ways to hide from them. In CAR-T therapy, a patient's T cells are modified to carry a chimeric antigen receptor (CAR) on their surface: an engineered protein that recognises a specific molecule on cancer cells.

The most common targets are CD19, a protein on B cells including those in B-cell leukaemias and lymphomas, and BCMA, a protein on plasma cells in multiple myeloma. Once infused back into the bloodstream, the CAR-T cells multiply, seek out cells carrying the target and kill them. That is why the treatment is sometimes called a "living drug".

CAR-T belongs to the wider family of cancer immunotherapy and to modern approaches to cancer treatment.

Which conditions is it used for?

The CAR-T products currently approved in Europe and the United States are for certain blood cancers:

• B-cell acute lymphoblastic leukaemia (B-ALL) in children and young people, and with some products in adults, when the disease has relapsed or not responded to treatment.
• Diffuse large B-cell lymphoma and other aggressive B-cell lymphomas after earlier treatment has failed, and for some patients as second-line treatment.
• Follicular lymphoma and mantle cell lymphoma that have relapsed or are resistant.
• Multiple myeloma after several previous lines of treatment.

Exact indications are set by regulators, in the EU the European Medicines Agency, and may widen over time. Whether a patient is suitable is decided by a haematologist in a specialist centre after a thorough assessment.

The treatment step by step

1. Assessment: examination and tests of the heart, lungs, kidneys and for infections, plus imaging such as PET/CT (see our guide to diagnosis and tests), followed by a team discussion.
2. Leukapheresis: a machine similar to those used for blood donation collects white blood cells over a few hours.
3. Manufacturing: in a specialist laboratory the T cells are genetically modified, usually with a viral vector, and multiplied. This typically takes several weeks, and "bridging" treatment may be needed to control the disease meanwhile.
4. Lymphodepleting chemotherapy: a short course of chemotherapy a few days before infusion "makes room" for the CAR-T cells.
5. Infusion: the CAR-T cells are given through a drip, much like a blood transfusion, over about half an hour.
6. Monitoring: patients are watched closely for the first weeks, often in hospital, and are usually asked to stay near the treatment centre for around four weeks.

Possible side effects

Cytokine release syndrome (CRS)

As CAR-T cells activate they release large amounts of signalling proteins called cytokines. This can cause fever, fatigue, a fast heart rate and low blood pressure and, in severe cases, breathing difficulties and organ failure. It usually starts within the first days after infusion. Teams follow standard protocols and use medicines, including interleukin-6 blockers and steroids, to control it.

Neurological side effects (ICANS)

These may include confusion, difficulty speaking or writing, drowsiness and tremor, and less often seizures or brain swelling. They are usually temporary but need careful monitoring. For this reason, patients need a carer with them and must not drive for several weeks after treatment.

Other risks

• Low blood counts, sometimes for a long period.
• Infections: CAR-T cells also destroy healthy B cells, lowering antibody levels, so immunoglobulin replacement and preventive medicines may be needed.
• Secondary cancers: regulators have added warnings about rare T-cell cancers after CAR-T therapy, so patients are followed up long term.
• Product-specific effects, such as delayed movement or nerve problems with some BCMA-targeted therapies.

What results can be expected?

Among patients with B-cell leukaemias and lymphomas that have not responded to other treatment, CAR-T therapy leads to complete remission in a proportion, and for some of them the remission is long-lasting. In multiple myeloma responses are often deep, but in many patients the disease eventually returns. Outcomes depend heavily on the type of disease, previous treatment and general health, so doctors avoid generalisations and discuss realistic prospects with each patient. CAR-T therapy is not a guaranteed cure.

Where CAR-T is heading

• Solid tumours: CAR-T for lung cancer, breast cancer, liver and brain cancers is being studied, but it is harder because these tumours offer fewer suitable targets and suppress the immune system around them.
• Earlier treatment: using CAR-T earlier in the course of disease is under investigation.
• "Off-the-shelf" (allogeneic) CAR-T from donors, aiming for faster access without waiting for manufacturing.
• Autoimmune diseases: early studies are exploring CAR-T against B cells in severe autoimmune conditions such as systemic lupus.
• Related approaches: CAR-NK cells, TCR therapies and bispecific antibodies.

These directions are promising but are still being evaluated in clinical trials.

When to talk to a doctor

If you or someone close to you has leukaemia, lymphoma or multiple myeloma that has come back or is not responding, ask the haematologist whether CAR-T therapy or a clinical trial might be an option. The earlier this is discussed the better, as preparation and manufacturing take time. After CAR-T treatment, contact your team or emergency services immediately for fever, chills, breathlessness, dizziness, confusion, trouble speaking, severe headache or seizures, and always say that you have had CAR-T therapy. For complex decisions, a second opinion is sensible.

CAR-T therapy abroad and in Türkiye

CAR-T therapy is delivered in a limited number of accredited centres with experience in bone marrow transplantation, and access varies between countries. Some patients from Bulgaria and elsewhere in Europe therefore seek a consultation abroad, including at large hospital groups in Istanbul. If you consider this, check whether the centre has experience with the specific product and indication, how complications are managed, how long you must stay near the hospital (usually several weeks) and how long-term follow-up will continue at home. New City Clinic can coordinate the consultation, hospital, hotel, transfers and interpreter, but the decision should be made together with your own haematologist.