Patients with the most aggressive forms of the blood cancer multiple myeloma can live significantly longer when their treatment is tailored to their disease, according to new long‑term results from a major UK‑led clinical trial.

The findings come from extended follow‑up of the OPTIMUM (MUKnine) trial, led by scientists at The Institute of Cancer Research, London, alongside colleagues at The University of Leeds, The Royal Marsden NHS Foundation Trust and hospitals across the UK.

Results of the study, published in The Lancet Oncology, show that a personalised, risk‑adapted treatment strategy improves survival for patients with high‑risk myeloma — a group historically associated with rapid relapse and poor outcomes.

At around six years, about seven out of 10 patients (69.1 per cent) on the OPTIMUM trial were still alive, compared with around 40 per cent on standard therapy, showing a clear survival benefit.

Multiple myeloma is a cancer of the plasma cells, with around 5,900 new cases diagnosed each year in the UK. Although modern treatments mean more than half of patients now survive at least five years, around 20–25 per cent have aggressive disease that responds poorly to conventional treatment.

Earlier analyses from OPTIMUM trial, which was funded by Myeloma UK and The David Forbes Nixon Foundation, with support from The Royal Marsden Cancer Charity and the National Institute for Health and Care Research, showed promising early outcomes for this group of high‑risk patients. However, the new long‑term data now confirms that these benefits are durable.

More than half of patients (53.8 per cent) on the trial remained progression‑free at six years, compared with fewer than one in five (17.6 per cent) patients in a matched external control group from the Myeloma XI trial.

By the end of the follow‑up period, median survival had not been reached for OPTIMUM, meaning more than half of patients were still alive. In contrast, the median survival for the patients on standard therapy was about 57 months (just under five years).

The researchers also examined outcomes within specific high-risk subgroups to understand which patients benefited most from the personalised approach.

One subgroup comprised patients who had been identified as high-risk by gene expression profiling using the MMProfiler SKY92 test, who would not otherwise have been identified as high risk.

The results showed that 62.3 per cent of these patients who were given personalised risk-adapted treatment were still alive and progression free at six years compared with 20.3 per cent of patients who had received conventional treatment.

Gene expression profiling is not routinely available in the NHS, meaning that many of these patients are currently diagnosed as having “standard‑risk” myeloma and may not receive optimal treatment from the outset.

The findings highlight the importance of modern molecular diagnostics to ensure that patients receive the most appropriate therapy when they are diagnosed.

The study also identified a smaller subgroup of patients with extremely complex genetic risk, defined by three or more high‑risk genetic abnormalities, whose outcomes remained poor despite intensive treatment. The authors say there is a clear unmet clinical need for this group and should be prioritised for trials of new treatment approaches.

The OPTIMUM trial used five medicines that were already licensed and widely used in the NHS (daratumumab, cyclophosphamide, bortezomib, lenalidomide, and dexamethasone) but applied them in a different way — intensifying treatment upfront and continuing combination therapy for as long as the disease remained controlled.

The results support a growing shift towards precision medicine in myeloma and underline the importance of molecular testing to guide treatment decisions, aligning with ambitions set out in the NHS 10-year cancer plan.

The MMProfiler SKY92 test is currently being evaluated through NICE’s diagnostic technology assessment programme.

Professor Martin Kaiser, Professor of Molecular Haematology at The Institute of Cancer Research, London, 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.”

“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.”

Dr Andrew Hall, Principal Statistician at The University of Leeds, said:

"The OPTIMUM trial is a powerful example of what can be achieved through collaborative academic research. Bringing together the NHS, academic researchers and charities from across the UK enables ambitious studies that generate the evidence needed to improve care for patients. Continued investment in UK academic clinical research is essential if we are to deliver more advances like this.”

Professor Kristian Helin, chief executive of The Institute of Cancer Research, London, 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. 

“Our mission is to develop smarter, more precise approaches to cancer treatment so that more people can live longer and healthier lives and studies like OPTIMUM show that this vision is becoming a reality. But they also point to something we must act on now: too many high-risk patients are still not being identified through routine testing. Closing this diagnostic gap will be essential if every patient wherever they are treated, is to benefit from the kind of tailored care these results make possible.”

Dr Sophie Castell, chief executive at blood cancer charity Myeloma UK, said:

“Professor Kaiser’s research is a major step in bringing forward truly personalised treatment and could transform the lives of thousands of people affected by myeloma. We firmly believe that advanced genetic testing and adapting treatment accordingly is the future of myeloma care and we’re very proud to be funding this work. 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.”

CASE STUDY

‘I was told that I might only have two years to live’

Ken Theobold, 76, was diagnosed with high-risk myeloma in 2018 after a routine blood test showed something unexpected. After initial treatment and a stem cell transplant elsewhere, he was referred to The Royal Marsden and joined the MUK Nine trial.  

"After my diagnosis I was told that I might only have two years to live, which was incredibly difficult to hear. 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.

“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.

"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."

Source: The Institute of Cancer Research, London