A new trial is assessing whether a type of CAR-T treatment may be safe for people with Systemic Lupus Erythematosus (SLE).

 

What is CAR-T cell immunotherapy?

CAR-T cell stands for “Chimeric Antigen Receptor T-cell” and is a type of immunotherapy.

The immune system has lots of different types of cells, including T cells and B cells. B cells produce antibodies that signal to other parts of the immune system, such as T cells, to destroy infections, disease, and damaged cells. In lupus, the B cells produce autoantibodies which means the immune system mistakenly attacks the body’s own tissues.

CAR-T cell therapy involves collecting a patient’s T-cells and modifying them so that they can recognise and destroy B cells. The idea is that the T cells could destroy the B cells that create the autoantibodies, so the immune system stops attacking the body’s own tissues, which reduces the inflammation and damage caused by lupus.

It has been used as an immunotherapy treatment for some types of blood cancer, and was tested in a small (unrelated) study with people with SLE in 2022.

What is this study about?

This study is a “phase 1” trial. A Phase 1 trial is done with a small group of people to test the safety of a treatment and how well it is tolerated. If the Phase 1 trial goes well, then a treatment may be tested in larger trials with more people to see how effective it is or to compare it with other treatments. Some treatments do not go past Phase 1.

This trial is being done by a biotechnology company called Autolus, who are testing their CAR-T treatment. They want to find out if it could be safe and effective in SLE. They are including up to 12 people with SLE in the trial.

Who can take part?

People may be able to take part if they are:

• Aged 18 or over.
• Have a diagnosis of SLE that has not responded to other treatment (called “refractory SLE”) and it is considered to be severe by their doctor.
• Are not pregnant or breastfeeding, and willing to use contraception and not have a child for 12 months after having the treatment.
• Have test results on their liver, heart, lung, and kidney function within a particular range.
• Are able to stop taking some specific medications during the study.

The detailed list of eligibility criteria would be discussed with you to check you are able and happy to take part.

What will happen if I take part?

If you took part and remained eligible throughout the study, you would receive the CAR-T treatment and be monitored, including a stay in hospital. Before you signed up, you would be given full details of what the study involves to make sure you were happy to continue. The study includes:

1). Initial screening to make sure you are eligible, including blood and urine tests, a medical assessment, and questionnaires. There would also be these kinds of screening checks in between other steps of the trial.

2). Approximately 4 weeks before the treatment, you would have “leukapheresis”, which is a process to collect white blood cells from your blood. These blood cells are then used to make your treatment.

3). Five days before the treatment, you would have “lymphodepletion”, which is the process of reducing the number of white blood cells in your body to make “space” for the CAR-T treatment. You would be given cyclophosphamide and fludarabine for lymphodepletion.

4). The CAR-T treatment would be given as a one-time infusion in hospital.

5). You would need to stay in hospital for at least 10 days to be monitored. This could be longer if the doctor felt you needed more monitoring.

6). There would be blood and urine tests, medical assessments, and questionnaires to see whether and how the treatment was working in your body. These would be on day 15, 22, 25, and 28 after receiving the treatment, and once a month for a year.

You would not be able to receive the infusion if any of the screening assessments meant you were not eligible. It’s also possible that you would not be able to receive the treatment infusion as planned if not enough cells were collected or grown in the laboratory after leukapheresis to produce the required dose.

At the end of this study, the research team would then invite you to participate in a long-term study where they measure the effects for 15 years after the treatment infusion with screening visits once or twice a year.

Are there any risks to taking part?

The study team would talk though any potential risks to make sure you understand them before you decide whether to take part. There are two main risks to taking part:

1. You have to stop most of your SLE treatments when you take part, and are only allowed to take no more than 10mg of prednisone during the study. This could increase your symptoms.

2. There may be side effects from the CAR-T treatment. Some possible side effects could include:
• Cytokine release syndrome (CRS)
• Complications of the nervous system (neurotoxicity)
• Allergic reactions during the infusion
• A weakened immune system
• Low blood cell counts

How do I find out more?

If you are interested in finding out more, you can find more details on the ClinicalTrials.gov page for the trial.

If you are interested in taking part in the trial, you need to speak to your rheumatologist to be referred, you cannot refer yourself or contact the trial team yourself. There are two trial sites in the UK (UCLH in London and Manchester Royal Infirmary), but you can be referred into the trial from wherever you live in England. Your rheumatologist needs to contact the trial team, and they can find the contact details on the ClinicalTrials.gov page for the trial.

 

Lupus UK received a fee from Autolus for the time spent to create this article. Autolus checked the article to make sure the facts were correct, but Lupus UK had editorial control and remain independent of Autolus.