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IMS 2026 | Genetic risk factors and outcomes in ultra-high-risk multiple myeloma
Martin Kaiser, MD, FRCP, FRCPath, The Royal Marsden NHS Foundation Trust, London, UK, discusses an exploratory genetic analysis from the Phase II OPTIMUM/MUKnine trial (NCT03188172) evaluating additional risk factors within ultra-high-risk newly diagnosed multiple myeloma. He highlights how the accumulation of adverse markers, including biallelic del(1p), TP53 abnormalities and high-risk gene expression, identified patients with particularly poor outcomes despite intensified treatment, while some patients with fewer high-risk features experienced favorable long-term outcomes. This interview took place at the 23rd International Myeloma Society (IMS) Annual Meeting in Glasgow, UK.
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Transcript
So we’re really, really honored and are grateful that our abstract on the OPTIMUM/MUKnine trial exploratory genetic analysis has been accepted for the plenary here at the IMS session. It’s actually the work of a clinical fellow, Dr. Beer, who has looked into which factors, genetic and genomic factors, are within the group of already ultra-high-risk patients, that are yet leading to potentially better or worse outcomes within that group...
So we’re really, really honored and are grateful that our abstract on the OPTIMUM/MUKnine trial exploratory genetic analysis has been accepted for the plenary here at the IMS session. It’s actually the work of a clinical fellow, Dr. Beer, who has looked into which factors, genetic and genomic factors, are within the group of already ultra-high-risk patients, that are yet leading to potentially better or worse outcomes within that group. We looked at factors that are the classical cytogenetic factors, but also gene expression, high-risk, and biallelic deletion or deletion and mutation of 1p and TP53. So by actually assigning effectively a count to each of these markers, we can definitely see that those patients that have accumulated several of these adverse markers, four or five of these markers together, have still, even with intensified treatment, a really unsatisfactory outcome. In turn, we also identify a group of patients within what we consider ultra-high-risk disease who have benefited drastically, really, really fantastically, from intensified treatment. Patients with just two points, so just two high-risk cytogenetic abnormalities, but no genetic gene expression high-risk or no mutation of TP53 have done really, really well there. Four-year progression-free survival was 100%. We have not seen this before in an ultra-high-risk group. So we really think that these advanced genetic tests at baseline are something we should really advocate for for patients. This should include gene expression profiling as well. It’s us as a scientific community that have to advocate for this to bring it to our patients because it really helps us already to tell the patient then whether to maybe go into a current treatment that is intensive because it benefits them very likely or maybe whether to consider a clinical trial because we do know that the current treatments are just not optimal for them.
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