iwHRMM 2024 | Extramedullary disease in multiple myeloma: biology, the potential role of AI, and more

Faith Davies:
Hi, my name is Faith Davies and I’m here at IW High Risk Multiple Myeloma in Charleston. And we’ve just finished a really exciting session about extramedullary disease in multiple myeloma. And I’m here with my colleague.

Mehmet Samur:
Mehmet Samur from Dana-Farber.

Faith Davies:
So I thought I’d just start off saying a little bit about some of the clinical data that we saw. And there was lots of discussion about the differences between paramedullary or paraosseous disease and true extramedullary disease. And how in many of the clinical trials now, the patients that truly have the poor outcome are those with the extramedullary disease and that potentially those patients that have the paraosseous disease, they may have a poorer outcome, but majority of studies now are showing that those differences are actually much slimmer. There was also a lot of discussion, Eleni from Bologna gave a great talk discussing about imaging in extramedullary disease and how PET imaging can be good to pick up extramedullary disease, but also how we can use diffusion-weighted MRI. And we should truly be trying to use a functional method to determine it, particularly when we come to response. And she also had some lovely new data to suggest that we shouldn’t just be looking for the disappearance of the signal and the fact that the lesion will get smaller, because for some of the lesions that are maybe involved with bone, it can take a long time for that lesion to repair itself. And actually, it may be more important just to look for the disappearance of the signal. And I think it brought up all sorts of discussions about maybe AI and how we could use that.

Mehmet Samur:
So I mean, from both sides, clinical perspective and the translational perspective it was a very fruitful session, and using the question from the audience specifically related to using AI in imaging and then how we can take what we are learning from other cancers beyond myeloma was very interesting. I think there’s definitely a place where we can use these new technologies and imaging to detect extramedullary disease, its location, its volume, the number of nodes we see, how it correlates with different clinical features. I think there’s a great future and it looks like maybe not today but in the near future we will be seeing some of these really coming on the research side and they’re fruitful. We will be seeing also it’s going beyond the research coming maybe to our clinical applications. But beyond the imaging, there was also very good data on genomics, how it shows certain regions are being enriched compared to bone marrow. Maybe those genomic changes, the enrichment of the genomic alterations will also guide us understanding what makes myeloma even more aggressive, let it slip the bone marrow and then cause all these extramedullary sites. And then the similar discussion was also around the microenvironment and stroma cells where we touched not just the changes on the myeloma cells and the plasma cells, but also their environment, maybe letting them slip through their environment and these cells are becoming hard to handle in the next step. So I think the accumulated data in the field is good, but obviously this is a field I think a lot of us are just beginning to understand, look with the new technologies and gaining more information on it.

Faith Davies:
Yeah. So as you say, I think some of the data that interested me was the genomic side and how many of the extramedullary disease is much more complex maybe than we expected. So lots of complex abnormalities. But then I think your good self, as well as some of the other people there were talking about how in the extramedullary disease, the microenvironment cells were actually different. So we maybe had more exhausted T-cells, maybe more macrophages and things like that.

Mehmet Samur:
Yeah, I mean, there is some evidence that when you look at the extramedullary sites and the bone marrow, their microenvironment cells may be becoming different. Like I was giving an example specifically to macrophages. But I think there are still also questions we don’t clearly know yet. And that’s where we are going to go next, I believe, is how complex genomic alterations are actually related to differences in the microenvironment cells. When the cells become, in other words, when the cells become more complex, are they actually releasing some crosstalk that suppress the microenvironment? And then that microenvironment changes, eventually leading cell adhesion disparities, and then let them go outside of the bone marrow. So I think there are still lots of things we need to think and see how it actually translates to translation or research and maybe in the clinic.

Faith Davies:
Yeah, I think it also comes back to what you were saying earlier about the AI side of things. I can imagine we’re not just going to be having the AI for reading our scans, but we’re going to need some form where we can put our data in and say, this is what the plasma cells in the bone marrow genetics. This is the immune system in the bone marrow, what we know about that. But then we’ve also got this complexity about those interactions in the extramedullary disease.

Mehmet Samur:
Exactly. Like when you see the patients in the clinic, I believe you’re accumulating a lot of data from imaging to lab side to the genomics. And in most settings today, those are sitting in independent domains. I think that’s where we need to find ways to integrate all the information. And then we just need to do it in longitudinal perspective, not at a single time point. There was also a discussion, I think, at some point about the MRD negativity and positivity. So, you know, that’s not something you can measure at the diagnosis, but there are a lot of other features we can measure through the treatment, through the course and then you know eventually find one integrative approach that we can learn from all different data set and come up with maybe dynamic risk assessment models over the time.

Faith Davies:
Yeah that’s brilliant. Thanks so much for spending some time with me and thank you, you guys for listening and we’ll sign off for iwHRMM.