A new trial found that a combination of five existing drugs fights against bone marrow cancer for longer in patients.
The five-drug cocktail, along with a stem cell transplant, allowed people with multiple myeloma – a type of bone marrow cancer – to live longer before their disease progressed than those who received the standard care.
A team at The Institute of Cancer Research, London, and the Clinical Trials Research Unit at the University of Leeds adopted a new high-speed trial methodology, testing the five-drug combination against the findings of an earlier study. This method obtains the results faster for the eventual benefit for patients with bone marrow cancer.
Their findings were presented at the American Society of Hematology Annual Meeting.
Fighting bone marrow cancer
The ‘MUK Nine OPTIMUM’ trial used a highly innovative methodology to the first tailored approach for people with the highest risk forms of myeloma – whose outcomes from treatment are currently poor.
The study demonstrated the benefit of combining drugs with different mechanisms of action to combat cancer’s ability to evolve and become resistant to treatment.
The five drugs in the combination included bortezomib, lenalidomide, daratumumab, dexamethasone and cyclophosphamide chemotherapy. They are all individually licensed and in clinical use. That means the combination has the potential to receive streamlined approval and become available to patients quickly.
Certain genetic changes can make multiple myeloma – a type of bone marrow cancer – more aggressive, less responsive to treatment and likely to relapse more quickly. Ultra-high-risk patients have particularly unfavourable genetic signatures, with studies suggesting they are at very high risk of their disease relapsing within the first two years from diagnosis. In contrast, the majority of other patients now stay in remission for five years or longer.
Currently, there is no tailored treatment approach for these high-risk patients, and their outcomes remain poor.
Study leader Dr Martin Kaiser, Team Leader in Myeloma Molecular Therapy at The Institute of Cancer Research, London, and Consultant Haematologist at The Royal Marsden NHS Foundation Trust said: “We know that patients with multiple myeloma who have ‘ultra-high risk’ genetic signatures have particularly aggressive cancers that fail to respond to standard treatment. In this study, we have identified a new five-drug combination that can keep myeloma at bay for longer in these patients. Our study shows the benefit of genetic testing in patients with myeloma to identify those at the highest risk since we now have a new and better treatment option for these people.
“All these drugs are already individually licensed and available, so we know they are safe, and that means the new combination could potentially be made available for patients quickly. I hope the NHS will consider our data as soon as possible.”
The OPTIMUM trial
The OPTIMUM trial involved 107 patients with high-risk myeloma recruited between 2017 and 2019. The results compared survival outcomes from OPTIMUM patients who received the new five-drug combination with survival outcomes in the Myeloma XI (MyXI) trial, who received carfilzomib, lenalidomide, cyclophosphamide and dexamethasone.
Patients from the OPTIMUM trial were more likely than MyXI patients to live longer, during and after treatment, before the bone marrow cancer progressed, and symptoms worsened. At 18 months, 82% of OPTIMUM patients had stable disease unlikely to progress in the immediate future, compared with 67% of MyXI patients.
The new findings represent a significant advance for patients with high-risk myeloma. It has highlighted the need to tailor therapy to the genetic make-up of each patient’s cancer, which is currently not done routinely.
Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, London, said: “Until now, patients with the highest risk forms of multiple myeloma have had no tailored treatment options, even though we know that they are likely to relapse on existing therapies. This study represents an important step forward, moving to more effective treatment of these patients.
“This exciting trial is also a first of its kind – using sophisticated statistical analysis to compare results with those from an earlier study rather than a control group. The new trial methodology has great potential to get much-needed new therapies to the clinic faster, and it also lowers trial costs.”