A clinical trial of a personalised therapy for blood cancer, led by researchers at UCL and University College London Hospitals, has been expanded enabling new groups of patients with a wider range of blood cancers to now receive the treatment.
The new type of CAR T-cell therapy - where a patient’s own immune system is ’reprogrammed’ in order to fight their cancer - has already been shown to have promise for adult patients with a type of blood cancer called relapsed B-cell acute lymphoblastic leukaemia (B-ALL).
Now the therapy is being given to patients with relapsed/refractory B-Cell Non-Hodgkin’s Lymphoma (B-NHL) and chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL).
Early indications suggest patients are responding to the treatment and that it is tolerated well but full trial results are not yet published.
CLL is the most common type of blood cancer and accounted for around 1% of all new cancer cases in the UK between 2016 and 2018. Around 3,800 people in the UK are diagnosed with CLL every year - around 10 a day.
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.
The therapy is being given 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.
Participants to the trial are being recruited nationwide including at The Christie NHS Foundation Trust in Manchester.
What is CAR T-cell therapy?
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 giving them back to the patient via infusion.
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.
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 two challenges.
Professor Karl Peggs, ALLCAR19 Chief Investigator and Director of the Sir Naim Dangoor Centre for Cellular Immunotherapy at UCLH, said: "We are delighted to extend this promising therapy to other groups of patients with high unmet clinical need and to see early evidence of clinical activity combined with good tolerability."
Trial investigator Dr Claire Roddie, Associate Professor at UCL Cancer Institute and consultant haematologist at UCLH, said: "In B-ALL we found that this treatment could allow patients to have long-term remission, and replicating these results in CLL and other cancers would offer great hope to even more patients."
Dr Martin Pule (UCL Cancer Institute), who leads the UCL CAR T-cell programme, said: "A large focus of our work has been on minimising the toxicity associated with CAR T therapy while maximising the persistence of CAR T-cells in the body. By doing this we hope the treatment will be able to benefit more and more patients."
Trial clears cancer for lymphoma patient
Robin Edwards, a patient at The Christie NHS Foundation Trust in Manchester, who was first diagnosed with chronic lymphocytic leukaemia (CLL) a decade ago, is now free of the disease thanks to the treatment he underwent on the clinical trial.
Robin, 66, a retired IT specialist from Buxton in Derbyshire, is one of the first people in the UK to be given CAR T therapy for CLL.
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 four years. But when his CLL progressed in 2021, he was offered CAR T therapy as part of the ALLCAR19 trial.
The treatment involved taking a sample of Robin’s blood, sending it to a laboratory in London where the T cells are genetically modified over a five-week period. The manufactured blood cells were then then put back into his body through two intravenous infusions.
Robin underwent the therapy earlier this year, which involved 30 days in hospital at The Christie while his body’s own immune system attacked the cancer. Thankfully the treatment worked and three months after treatment he is in complete remission with no signs of cancer.
Robin, who enjoys Morris dancing, explained, "It might sound strange, but I see The Christie as a happy place. I totally trust the team. They wanted to treat my cancer 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."
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 received this treatment for CLL in the UK."
"He has had a terrific response and is 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 don’t respond to conventional treatment."