A patient at The Christie NHS Foundation Trust in Manchester, who was first diagnosed with chronic lymphocytic leukaemia (CLL), the most common type of leukaemia, a decade ago, is now free of the disease thanks to an innovative treatment he underwent on a clinical trial.
Robin Edwards, 66, a retired IT specialist from Buxton, is one of the first people in the UK to be given CAR-T therapy for CLL as part of the ALLCAR19 trial, run by a team at University College London Hospitals NHS Foundation Trust (UCLH) and UCL, in collaboration with UK-based CAR T cell therapy company Autolus Therapeutics.
CAR T-cell therapy involves collecting a patient’s own white blood cells (T-cells, responsible for fighting infection), ‘reprogramming’ them in the laboratory to seek and ‘fight’ the cancer cells and give them back to the patient via infusion. This therapy has been available in the UK since 2018 but is currently only licensed for treatment of a small number of aggressive blood cancers.
For the ALLCAR19 trial, patients have their T cells genetically modified with a new type of CAR called obecabtagene autoleucel or obe-cel*. This treatment programmes immune T cells to make an artificial protein called a CD19 chimeric antigen receptor (CAR) on their surface, directing them to specifically recognise cancerous cells.
CLL is the most common type of leukaemia. According to Cancer Research UK data, around 3,800 patients are diagnosed in the UK every year; that's 10 every day (2016-2018). CLL accounted for 1% of all new cancer cases in the UK in 2016 to 2018. Patients are commonly diagnosed with relatively asymptomatic disease which is managed with observation although most will ultimately require treatment. The last decade has been marked by considerable progress in CLL therapies however treating patients with hard to treat or relapsed disease is an area of unmet need.
Having first discovered he had cancer in 2012, Robin initially had standard chemotherapy to keep the cancer at bay. In 2016, he signed up for a clinical trial which took him into remission for 4 years. But when his CLL progressed in 2021, he was offered CAR-T therapy as part of the national ALLCAR19 clinical trial.
The treatment involved taking a sample of Robin’s blood, sending it to a laboratory at the UCL Cancer Institute in London where the T cells were genetically modified over a 5-week period. The manufactured blood cells were then then put back into his body through two intravenous infusions.
Robin underwent the therapy in May last year (2022), which involved 30 days in hospital at The Christie while his body’s own immune system attacked the cancer. Thankfully the treatment worked and 3 months after treatment he is in complete remission with no signs of cancer.
Robin, who enjoys Morris dancing, gardening and walking explained, “I feel confident and relaxed at The Christie, totally trusting the excellent team who support me. They wanted to treat my CLL early before we got on the back foot and remedial action was needed. I didn’t think CAR-T was on the cards for a patient like me, but thanks to the clinical trial I now have no detectable disease which is fantastic.”
Photo: Robin with his 2 young grandchildren
Professor Adrian Bloor, consultant haematologist at The Christie said: “Whilst CAR-T therapy has become established as a standard treatment for some blood cancers, it is uncertain how effective this is for treatment of CLL. Robin is the first CLL patient treated with CAR-T therapy at The Christie and one of just a handful of patients who have been received this treatment for CLL in the UK.
“He has had a terrific response and currently completely clear of the disease, but it is still early days and we will need more follow up to assess how effective this is in the longer term. This is a pioneering treatment and hopefully has the potential to transform the outlook for patients with CLL that doesn’t respond to conventional treatment.”
Any patients interested in taking part in clinical trials should discuss this option with their consultant or GP. Not all patients will fit the criteria for a specific trial. While clinical trials can be successful for some patients, outcomes can vary from case to case.
* Obe-cel was designed by scientists in Dr Martin Pule’s lab at UCL Cancer Institute– in work that is supported by the National Institute for Health and Care Research UCLH Biomedical Research Centre (BRC). Dr Pule is Chief Scientific Scientific Officer of Autolus Therapeutics.
Obe-cel is intended to overcome two common constraints associated with ‘first generation’ CAR T-cell therapies. One problem was that the immune system became over-activated, causing a toxic reaction called ‘cytokine release syndrome.’ The other problem was that T-cells were not able to persist in a patient’s body.
Phase 1 trial findings for patients with B-ALL suggested this second-generation form of CAR T-cell therapy is successfully able to overcome these 2 challenges.