Personalised, risk-adapted therapy doubles six-year survival in high-risk multiple myeloma
核心洞察
Long-term results from the Optimum (MUK Nine) trial show 70% of high-risk myeloma patients on personalised treatment were alive at six years, versus around 40% on standard therapy.
Progression-free survival at six years reached 54% with the risk-adapted approach, compared with 18% for patients receiving usual care.
The trial, led by The Institute of Cancer Research, combined a stem cell transplant with five existing NHS drugs, adapted to each patient's molecular disease biology.
A blood cancer patient given just two years to live after a high-risk myeloma diagnosis in 2018 is still alive eight years later, following treatment on a groundbreaking trial investigating personalised, risk-adapted therapy. Ken Theobold, now 76, was diagnosed with high-risk myeloma after a routine blood test and enrolled in the Optimum (MUK Nine) trial, where long-term follow-up data now show that patients live significantly longer when their treatment is adapted to the molecular biology of their disease.
About 5,900 people are diagnosed with multiple myeloma (搜索) — a cancer of the plasma cells — each year in the UK, a quarter of which respond poorly to conventional treatment. "After my diagnosis, I was told that I might only have two years to live, which was incredibly difficult to hear," Mr Theobold said. "Joining the trial was an absolute no-brainer. If there was a chance it could help me and help future patients, I wanted to be part of it."
The study, led by experts at The Institute of Cancer Research (ICR), London, involved 107 people with newly diagnosed high-risk multiple myeloma (搜索) — previously known as ultra-high-risk myeloma. The ICR, together with experts from the University of Leeds, The Royal Marsden NHS Foundation Trust and hospitals across the UK, treated patients with a stem cell transplant and a combination of five medicines already used in the NHS: daratumumab, cyclophosphamide, bortezomib, lenalidomide and dexamethasone. Crucially, patients received these drugs in a different way, with intense treatment at the start and continuing combination therapy for as long as the disease remained controlled.
Mr Theobold was referred to The Royal Marsden and has been treated on the MUK Nine trial for the last eight years. "When I first joined the trial, I was taking five different drugs, which was quite intense but I have since moved to the maintenance part of the trial, which only involves two drugs," he said. "Today, I'm able to enjoy life with my wife, Brenda. We love travelling in our motorhome, and spending time with our five grandchildren is what matters most."
Long-term results from the trial, published in the journal Lancet Oncology, show a marked survival advantage. At around six years of follow-up, 70 per cent of patients who took part in the Optimum trial were still alive, compared with around 40 per cent on standard therapy. Some 54 per cent of patients on the trial remained progression-free at six years, compared with 18 per cent of patients who received usual care.
First author Martin Kaiser, professor of molecular haematology at the ICR and consultant haematologist at The Royal Marsden NHS Foundation Trust, said: "High-risk myeloma has traditionally been one of the toughest challenges we face, with patients often relapsing early despite the best available treatments. These long-term results show that when we adapt treatment to the biology of the disease, we can significantly extend survival for many patients who previously had very limited options."
Researchers also examined whether the personalised approach benefited people with specific subgroups of the disease. They used a test called MMProfiler SKY92, which identified people as high-risk by their gene expression. This gene expression profiling is not routinely available in the NHS, meaning patients who may be high-risk may not be identified as such, the ICR said. The study found that 62 per cent of this subgroup of patients given the personalised risk-adapted treatment were still alive and progression-free at six years, compared with 20 per cent of patients who had received conventional treatment. The ICR said the test is being evaluated by health regulators for potential use across the health service.
"This study also shows that some patients with aggressive disease are currently being missed because the necessary molecular tests are not routinely available. Identifying these patients earlier could allow us to tailor treatment from the start and change the course of their disease," Prof Kaiser said.
ICR chief executive Professor Kristian Helin said: "These results are a powerful example of how understanding the biology of cancer can transform patient outcomes. By matching treatment to the molecular features of each person's disease, we are beginning to outsmart cancers that were once extremely difficult to treat — and high-risk myeloma has long been one of the hardest to treat effectively."
Dr Sophie Castell, chief executive at blood cancer charity Myeloma UK (搜索), said: "Identifying which patients are more likely to benefit from a personalised approach to treatment has been shown to keep myeloma at bay longer and give people a better chance to live well with their disease."