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Oxford Myeloma Workshop 2025 | Using spatial transcriptomics to study focal lesions in multiple myeloma
In this interview, Leo Rasche, MD, University of Würzburg, Würzburg, Germany, and Niels Weinhold, PhD, Heidelberg University, Heidelberg, Germany, discuss focal lesions in multiple myeloma (MM), which are observed in around 80% of patients at the time of diagnosis. Dr Weinhold explains that focal lesions, accumulations of plasma cells, are often myeloma-defining events and can have clinical impact, especially when they become bone marrow independent. Dr Weinhold and Dr Rasche discuss spatial transcriptomics analyses of the T-cell compartment of these lesions, highlighting that similar features are observed both in paramedullary and extramedullary disease. This interview took place at the 5th Oxford Myeloma Workshop in Oxford, UK.
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Transcript (AI-generated)
Leo Rasche:
Niels, we both just had presentations on lesions, on myeloma lesions. And as you know, the vast majority of patients, like 80%, they have so-called focal lesions at the time of diagnosis. So what is a focal lesion? Can you explain it to us?
Niels Weinhold:
Yeah, so a focal lesion is a kind of accumulation of plasma cell in contrast to the kind of diffuse plasma cell infiltration we see in precursor stages, so actually these focal lesions are often myeloma-defining events...
Leo Rasche:
Niels, we both just had presentations on lesions, on myeloma lesions. And as you know, the vast majority of patients, like 80%, they have so-called focal lesions at the time of diagnosis. So what is a focal lesion? Can you explain it to us?
Niels Weinhold:
Yeah, so a focal lesion is a kind of accumulation of plasma cell in contrast to the kind of diffuse plasma cell infiltration we see in precursor stages, so actually these focal lesions are often myeloma-defining events. And what we learned from our time in Little Rock was that focal lesions per se often don’t have any kind of clinical impact. However, when we have multiple large focal lesions, there is a clear clinical impact and this is even more often seen when these plasma cells within these lesions become bone marrow independent and that was actually the major topic of Leo’s presentation today.
Leo Rasche:
Yes so, I think the focal lesion when it grows then sometimes it starts to grow bigger than the bone. Then we have what you call a breakout lesion that has a soft tissue component with it. That’s something what we also call paramedullary disease. What I was talking about was the frank extramedullary disease. That is a lesion that is somewhere in the organ, in soft tissue at the skin, but that has no contact to bone, and we know that has a very poor prognosis. And we did some spatial transcriptomics around these extramedullary lesions and we found that there is a skewed T-cell system or that we find some areas with an active functional T-cell compartment. But then within these lesions, it seems that they are exhausted. But is this feature only for extramedullary disease or can this be found in paramedullary disease as well?
Niels Weinhold:
Yeah, so the answer is yes. As Leo said, so this extramedullary disease is associated with a very poor outcome. And so my team was more interested in the question, what are actually the early steps? So what’s actually the first step in this path towards bone marrow independence as seen in extramedullary disease? So what we did was to get samples from surgery. So there were lesions actually broke the bone and there were fractures and there were surgeries to help these patients and we got sample material from these sites and used very similar methods that Leo’s team used to analyze extramedullary disease.
And what was really astonishing for us was that the phenotypes you observed in these lesions were very much similar to what Leo observed in extramedullary disease. So that means these massive changes in the composition of the microenvironment, but also in cell states within the microenvironment, seem to happen at that moment when plasma cells leave the bone marrow.
So we don’t understand the mechanism yet, but according to our so far descriptive studies, there are, as I said, massive changes in the microenvironment. And I guess the next step will then be to understand the interplay between tumor cells and the microenvironment in extramedullary disease, for example, versus these breakout lesions, to get a better idea what are actually the mechanisms that drive the very poor outcome in extramedullary disease.
This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.
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