A pensioner who was given just two years to live after being diagnosed with aggressive high-risk myeloma is still alive eight years later, after initially being told he had just two years to live, and then signing up for a pioneering treatment trial, reports The Independent.
At around six years of follow-up, 70% of the patients who took part in the Optimum trial were still alive, compared with around 40% on standard therapy: 54% of those on the trial remained progression-free at six years, compared with 18% of patients who received usual care.
Ken Theobold (76) was diagnosed in 2018 after a routine blood test. About 5 900 people are diagnosed with multiple myeloma – cancer of the plasma cells – annually in the UK, a quarter of whom respond poorly to conventional treatment.
Told that he might only have two years to live, he decided to sign up for a trial investigating the use of a personalised mix of cancer medicines for high-risk patients.
The study, led by the Institute of Cancer Research (ICR), London, involved 107 people with newly diagnosed high-risk multiple myeloma – previously known as ultra-high-risk myeloma.
Patients were given tailored treatment using a range of drugs. Long-term follow-up data have now shown that patients live significantly longer when their treatment is adapted to the molecular biology of their disease, the ICR said.
The ICR, along 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.
But patients were given these drugs in a different way, with intense treatment at the start and continuing combination therapy for as long as the disease remained controlled, the ICR said.
Theobold was referred to The Royal Marsden and has been treated on the MUK Nine trial for the past eight years. Long-term results from the trial have been published in the journal Lancet Oncology.
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 benefitted people with subgroups of the disease. They found that 62% of this subgroup of patients who were given the personalised risk-adapted treatment were still alive and progression-free at six years compared with 20% of patients who had received conventional treatment.
The scientists used a test called MMProfiler SKY92, which identified people as high-risk by their gene expression. This is not routinely available in the NHS, but is being evaluated by health regulators for potential use across the health service.
Study details
Induction and extended consolidation with daratumumab, cyclophosphamide, bortezomib, lenalidomide, and dexamethasone in patients with high-risk multiple myeloma (OPTIMUM/MUKnine): 5-year follow-up of a multicentre, externally controlled, phase 2 trial
Martin Kaiser, Rachel Phillip, Sarah Brown et al.
Published in Lancet Oncology on 7 September 2026
Summary
Background
High-risk multiple myeloma, defined by two or more high-risk cytogenetic abnormalities (HRCAs), high-risk gene expression profiling (GEP), or plasma cell leukaemia, remains associated with poor long-term outcomes despite quadruplet induction therapy. OPTIMUM showed that intensified induction, extended consolidation, and maintenance therapy after autologous stem-cell transplantation (ASCT) improved progression-free survival for patients with high-risk multiple myeloma. Here we report the 5-year follow-up of survival outcomes across molecular subgroups.
Methods
The multicentre, externally controlled, phase 2 OPTIMUM trial was conducted at 22 centres in the UK and enrolled patients aged 18 or older with newly diagnosed high-risk multiple myeloma or plasma cell leukaemia, measurable disease according to IMWG criteria, up to two previous induction cycles, and an Eastern Cooperative Oncology Group Performance Status of 2 or less. Participants received intravenous or subcutaneous daratumumab, oral cyclophosphamide, subcutaneous bortezomib, oral lenalidomide, and oral or intravenous dexamethasone induction at protocol specified doses before and after ASCT; melphalan–bortezomib during ASCT; consolidation part 1: daratumumab, bortezomib, lenalidomide, and dexamethasone; consolidation part 2: bortezomib, lenalidomide, and daratumumab; and maintenance lenalidomide and daratumumab until disease progression, unacceptable toxicity, or withdrawal. The trial used a Bayesian design and activity of treatment was compared with a molecularly matched external control cohort from the Myeloma XI trial. The primary endpoint was 18-month progression-free survival and has been previously reported. In this analysis, we report progression-free survival, progression-free survival 2 (time from registration until second disease progression or death, whichever occurred first), and overall survival at 5 years follow-up; and subgroup analyses by high-risk multiple myeloma features at entry (≥2 HRCAs, high-risk GEP, ≥2 HRCAs and high-risk GEP; and plasma cell leukaemia; subgroups selected post-hoc). OPTIMUM was registered with ClinicalTrials.gov (NCT03188172; active [not recruiting], with ongoing follow-up and maintenance).
Findings
Between Sept 29, 2017, and Sept 24, 2019, 108 participants with high-risk multiple myeloma were recruited to OPTIMUM and 107 were included in the analysis, with 120 genetically matched patients from the Myeloma XI trial (external control). Median follow-up was 71·1 months (IQR 66·9–77·7) for OPTIMUM and 117·8 months (98·3–128·6) for Myeloma XI. Progression-free survival (not reached [NR; 70·6–NR] vs 24·4 months [19·7–30·4]; HR 0·32 [95% CI 0·22–0·45]; p<0·0001) and overall survival (NR [NR–NR] vs 57·4 months [47·3–74·2]; HR 0·43 [95% CI 0·28–0·65]; p<0·0001) was longer in OPTIMUM than in Myeloma XI. Median progression-free survival 2 was NR (NR–NR) in OPTIMUM and 43·9 months (38·3–51·5) in Myeloma XI (HR 0·26 [95% CI 0·17–0·41]; p<0·0001). The survival benefit was consistent across high-risk multiple myeloma subgroups, except for patients with three or more HRCAs.
Interpretation
OPTIMUM shows sustained progression-free survival and overall survival improvement with risk-stratified extended therapy, supporting implementation of molecular diagnostics and tailored treatment in patients with newly diagnosed high-risk multiple myeloma.
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