UCLH has treated three patients with light chain amyloidosis (AL) using CAR T cell therapy in a clinical trial which is the first in Europe to test the safety and efficacy of this immunotherapy for this patient group.
AL is a rare but serious blood disease affecting around 500 people in the UK each year. It develops when abnormal immune plasma cells produce faulty “light chain” proteins that misfold and accumulate in tissues and organs. Without treatment, the condition can lead to organ failure and can be life-threatening. There is currently no cure.
The current standard treatment for AL amyloidosis is chemotherapy. While often effective, it involves weekly infusions for six months followed by regular maintenance therapy for up to 18 months. Chemotherapy can cause significant side effects, and the impact on patients’ quality of life during prolonged treatment can be considerable. Moreover, there is no licensed treatment for patients for whom chemotherapy does not work or in patients whose disease relapses, highlighting the urgent need for new options.
CAR T-cell therapy represents a fundamentally different approach. It involves collecting a patient’s own T cells (a type of immune cell) and genetically modifying them in a laboratory so they can recognise and destroy the abnormal plasma cells producing amyloid-forming proteins. The therapy targets proteins such as B-cell maturation antigen (BCMA), which are present on these harmful cells.
CAR T therapy has already proven extremely effective in treating multiple myeloma, a related blood cancer in which abnormal plasma cells also express BCMA.
The ALARIC trial, a non-commercial trial which is sponsored by UCL and supported by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at UCLH, aims to treat at least 12 patients over the next two years and will also shortly open in Leeds.
UCLH consultant haematologist Lydia Lee, who is also associate professor at UCL and principal investigator of the study, said: “This trial is an important first step in evaluating whether we can safely and effectively use this highly targeted therapy to eliminate the cells that drive this disease.”
UCL professor of medicine and haematology Ashutosh Wechalekar, the chief investigator of the study, said: “If we can interrupt the disease process at its source, we may be able not only to control the condition but also to improve patients’ quality of life.” Professor Wechalekar is also consultant haematologist at UCLH and the Royal Free London NHS Trust.
Tim Wiberg, 61, of Sheffield, is the third patient to receive CAR T-cell therapy as part of the ALARIC trial. When he was offered the opportunity to join the CAR T cell trial, he initially felt uncertain. After careful consideration, he decided to take part.
Tim said: “It feels like a genuine opportunity, not just for me, but for others who may face this diagnosis in the future. If my experience can help move things forward, then it feels worth sharing.”
ALARIC, as a non-commercial trial, is part of a broad and balanced portfolio of commercial and non-commercial trials at UCLH.
UCLH is working hard to improve the systems we have for non-commercial trials and commercial trials alike, to help drive efficiency and get them open to patients quickly.
Alongside commercial research, non-commercial trials such as ALARIC play a crucial role in UK life sciences, often tackling scientific or clinical questions which haven’t yet been considered or prioritised by industry, or testing interventions in patient groups who wouldn’t otherwise wouldn’t get the opportunity to access them. Non-commercial trials help improve lives, support economic growth, and support the NHS. These benefits were brought out in a report from the Association of Medical Research Charities last year.
Dr Nick McNally, Managing Director of Research, UCL/UCLH, said: “Non-commercial collaborative trials are critical in the overall ecosystem of research at UCLH and UCL, and are business as usual for us given the extensive scientific base we have at UCL and the well-developed partnerships we have with medical research charities and industry. With support from the UCLH BRC, we have the capacity and capability to set up, sponsor and manage novel phase one trials like ALARIC, thanks to our specialist sponsorship and regulatory experience in our Joint Research Office and in our nationally leading clinical trials units such as the UCL Cancer Trials Centre.
Prof Karl Peggs, UCLH Director of Research and Director of the NIHR UCLH Biomedical Research Centre, said: “I’m delighted to see the further expansion of our cell therapy portfolio enabling patients with clear clinical need but few therapeutic options to access some truly exciting novel trial opportunities. Our portfolio is considered the largest in Europe, combining our work with large pharma, our academic partners at UCL, and a number of UK-based early biotech companies. Our growth beyond cancer indications has only been made possible by the consistent support and funding provided by the NIHR BRC programme.”
Professor Allan Hackshaw, Director of the Cancer Research UK & UCL Cancer Trials Centre, said: “ALARIC is an example of successful cross-sector working in non-commercial research, with it being sponsored by UCL - which sponsors the largest number of advanced therapy cancer trials in the UK - and delivered via the Cancer Research UK and UCL Cancer Trials Centre.”
Image credit: Ramesh Pydiah/UCLH
