A UK-led clinical trial is set to test a new drug that could make cutting-edge cancer treatments safer and more accessible for thousands of patients with multiple myeloma, a type of blood cancer.
The trial, called TOPICAL, is led by The Christie NHS Foundation Trust and will take place at 5 other NHS hospitals in the UK.
TOPICAL will study whether an experimental anti-inflammatory treatment, known as POLB 001, can help prevent a common side effect called Cytokine Release Syndrome (CRS), a potentially dangerous immune reaction that can occur following powerful cancer immunotherapy treatments.
New immunotherapy treatments are transforming survival prospects for patients with blood cancers such as multiple myeloma, lymphoma and leukaemia. However, these treatments can trigger CRS, causing severe flu-like symptoms including high fever, dangerously low blood pressure, breathing difficulties and, in some cases, the condition can be life-threatening. Nearly a quarter of patients who develop severe CRS require intensive care.
The research is responding to growing demand for better ways to manage CRS, as more patients are being treated with immunotherapies. Studies show that over 70% of patients receiving some cancer immunotherapies are affected by CRS, highlighting an unmet need for proactive, preventative treatments.
Dr Emma Searle, consultant haematologist at The Christie, who is the chief investigator on the TOPICAL trial said: “Immunotherapy treatments are transforming survival rates for patients with difficult-to-treat blood cancers, but their use will continue to be restricted until we find a way to deliver them safely outside of specialist hospitals. Because of the risk of Cytokine Release Syndrome (CRS), which is unpleasant and can be dangerous, many patients can’t be treated near to home, which is a real problem. Many patients have to stay in hospital to receive immunotherapy, and some must travel long distances for treatment in specialist centres.
“If this new therapy can safely reduce the risk of CRS, it could help give these treatments near to or in peoples’ homes. Ultimately, our aim is to help more patients benefit from these life-saving therapies while reducing the burden of treatment on patients, families and the NHS."
Co-chief investigator Dr Rakesh Popat, a consultant haematologist at University College London Hospitals NHS Foundation Trust, said: “This study addresses an important question, whether patients can safely receive bispecific antibodies, particularly when they are dosed outside of hospital. While CRS in the most part is manageable, it leads to increased use of hospital resources and a higher burden of treatment on patients by the need for close monitoring and administration of treatment once it occurs. Having an oral preventative treatment can help reduce this and make the treatment easier for patients.”
The TOPICAL trial plans to recruit around 30 patients with relapsed or treatment-resistant multiple myeloma. Participants will receive POLB 001 alongside an approved bispecific antibody therapy. Patients will participate in the research at the National Institute for Health and Care Research (NIHR) Manchester Clinical Research Facility (CRF) at The Christie among other sites.
POLB 001 is being developed by London-headquartered biotechnology company Poolbeg Pharma (London Stock Exchange Listed, Ticker: POLB). The oral treatment works by targeting inflammatory pathways involved in CRS. Researchers will assess whether the treatment can prevent or reduce CRS following teclistamab treatment.
This investigator-led study is sponsored by the DIDACT Foundation, a partner organisation of Accelerating Clinical Trials Ltd (ACT), which is dedicated to improving outcomes for people with blood cancers.
Early results from the study are expected later this year.
The TOPICAL trial is contributing to the RISE programme, an £8m Manchester-led research project funded via the Medical Research Council Prosperity Partnership award, which is one of the biggest studies ever undertaken into the side effects of blood cancers.
Jason Walker - first patient recruited to TOPICAL trial
Christie clinical trials patient, Jason Walker, was just 45 when persistent back pain and double vision led to the devastating news in February 2014 that he had terminal stage 3 multiple myeloma, a type of blood cancer.
The now 57-year-old, from Longridge, near Preston, Lancashire, who runs a kitchen painting business, was diagnosed after tests revealed the cancer was all over his body, causing chronic bone pain particularly around his pelvic region. It was also found around his pituitary gland, where it was pulling on his optic nerve.
He was told the disease was incurable and treatment would focus on achieving long-term remission and extending his life. "It was a huge shock," Jason said. "One minute I was working, playing squash and getting on with family life and the next I was being told I had terminal cancer."
Jason underwent a course of intensive chemotherapy, while never taking a day off work, but 2 days after completing treatment, he suffered a heart attack while working in a customer's kitchen in Liverpool.
"I thought I had got through the hardest part and then I had a heart attack caused by a blood clot possibly due to the chemotherapy," he said. "It was frightening, but thankfully I recovered."
In the past decade, Jason has also undergone 2 gruelling but successful stem cell transplants and has remained determined to live life to the full.
Following treatment, Jason spent 5 years in remission and his life returned to normal. As well as squash, he enjoys padel and circuit training at the gym to keep fit.
However, in November last year he noticed several soft, spongy lumps on his head. "I knew something wasn't right," he said. Tests confirmed his myeloma had relapsed. After trying a 3-drug combination that his body couldn’t tolerate and made him so weak he couldn’t climb the stairs, he was referred to The Christie in Manchester to see if there were any clinical trials that he might be suitable for.
Jason has become the first patient to join the TOPICAL clinical trial, which is investigating whether an experimental anti-inflammatory drug can reduce the potentially severe side effects associated with a relatively new immunotherapy treatment for multiple myeloma. He has recently begun 14 cycles of treatment while continuing to work.
"This isn’t my first experience of taking part in research and I'd rather be on the trial than not," he said. "It gives you a security blanket. I feel very lucky to be on the trial at The Christie and I hope it works, not just for myself, but for the wider myeloma warriors out there. Any hope in a difficult situation is good. I feel blessed to be on the trial, it's like I've won something better than the lottery."
Jason said he has learned the importance of maintaining a positive outlook despite living with cancer for more than a decade. "I try to keep a positive attitude and laugh about cancer, but I do sometimes get mad and swear at it," he said. "Cancer doesn't care, but I won't let it get to me."
Jason and his wife, Michelle, have been married for 35 years and have 2 grown-up children. They are also grandparents to 7-year-old Harper, their son Oliver’s daughter.
Jason is particularly determined to beat the cancer again ahead of his daughter Abbey's wedding in Montenegro next May. "I need to get through this as I’m giving her away, and want to be well enough to walk my beautiful daughter down the aisle." he said.
Looking ahead, Jason hopes his involvement in the TOPICAL trial could benefit future patients as well as himself. "If taking part helps improve treatment for other people living with myeloma, that's something really worthwhile," he said. "I've been living with this disease for 12 years and you have to keep looking forward. I'll keep fighting and making the most of every day."