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iwHRMM 2025 | How RNA-based testing can be used to identify hidden risks in multiple myeloma
Martin Kaiser, MD, FRCP, FRCPath, The Royal Marsden NHS Foundation Trust, London, UK, shares insights into the importance of understanding the present state of myeloma cells beyond their genetic features and how RNA-based gene expression profiling can provide insights into this. Dr Kaiser highlights the value of self-developed tests, which can identify these hidden risks and capture more information. This interview took place at the 2nd International Workshop on High-Risk Multiple Myeloma (iwHRMM 2025), held in Charleston, SC.
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Transcript
The features that we know are associated with aggressive disease are very well defined as DNA or genetic features. They are kind of telling us what the genome has gone through in the past in terms of acquiring drivers, but also just general damage to the genome. And it’s kind of like telling us something about the past of the cell, but what we know less about is what is the present of the cell...
The features that we know are associated with aggressive disease are very well defined as DNA or genetic features. They are kind of telling us what the genome has gone through in the past in terms of acquiring drivers, but also just general damage to the genome. And it’s kind of like telling us something about the past of the cell, but what we know less about is what is the present of the cell. Now, in many other cancers, also in some of the lymphomas or blood cancers, we can identify whether, for example, the cell is at that moment growing and proliferating just by a simple immunohistochemical staining with Ki-67 or a similar marker, that has always been, unfortunately, not a reliable tool in myeloma. And actually, that’s where gene expression profiling comes in. It tells us the exact state of the cell that it is in at the moment in time when the biopsy is taken and can identify whether a large proportion of the cells in the sample are actually dividing at that moment or whether they are quiescent, dividing is clearly a sign of aggressiveness. Now, there are tests that are developed as patient-facing tests in diagnostic laboratories, one of them, for example, being the Sky92 test, which is important because we are normally having much higher hurdles. If we have self-developed a test, this test has actually gone through the validation process and can pick up these hidden risks. There are, of course, other hidden risks as well that, for example, are captured best by whole-body imaging, functional imaging. That’s yet another level towards a complete profiling of the patient’s predisposition. But we’re now able to capture already about 80% of patients that are at risk of early relapse by just integrating RNA into our standard of care DNA profiling process. Both are needed. None can completely supersede the other. But if we combine them, we have a very powerful tool at hand.
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