Role of Tumor Complexity and Microenvironment in the Development of Multiple Myeloma

At the 2023 Lymphoma, Leukemia & Myeloma Congress in New York, Gareth Morgan, MD, NYU Langone Medical Center, New York, New York, discusses the role that tumor complexity and microenvironment plays in the development of multiple myeloma. 

Transcript:

Good morning. My name’s Gareth Morgan. I’m a professor of medicine at NYU School of Medicine here in New York. I was at the LL&M meeting and had a great, great time, and was able to update people on some of the latest research that’s going on, [specifically] looking at the relationship between tumor complexity and the way the tumor develops. 

We've always concentrated on drivers of multiple myeloma that turn it from [monoclonal gammopathy of undetermined significance] (MGUS), a sort of benign, precursor condition, to myeloma itself, which is invasive, makes people anemic, damages the kidneys, and puts holes in the bones and forms lytic lesions. And so, understanding that process should allow us to manipulate it therapeutically.

We've learned lots about it. It's clearly driven by key genes such as RAS, NSD2, epigenetic genes that really can be identified to push the disease forward. But what's becoming more interesting, I think, is understanding how the disease has evolved, and it's made up of not just one clone of cells, but within that clone there are multiple subclones that interact with one another in a sort of Darwinian way. And with treatment, you can go into a deep remission. 

And if you don't go in a remission, look at relapse, it's clear that there's linear evolution. Whereas if you go into a deep remission, that when you look at relapse, there is very much clonal diversity, and many clones can give rise to the relapse. And when you look back, it looks as if the major contributor to relapse comes from focal lesions in the bone marrow where there are lumps of tumor rather than the diffuse tumor, which is kind of important because with new immunotherapies, you want to be able to get your treatment into these lesions to eradicate them completely.

The other side of the coin is looking at the interaction between the tumor cells and their drivers in the microenvironment. And it's very clear that the microenvironment changes at the same time as the tumor cells, and the two sort of co-evolve, one supporting the other. So, it's a real chicken and egg situation. But the important thing is, while we've always looked for targets in the tumor cells to treat cancer, I think you can look for targets in the microenvironment and use those microenvironmental targets as a way of controlling the cancer. And there are many of these targets. And the good thing is, many of them don't come with significant toxicity. So, breaking the tumor interaction with its microenvironment is another very exciting way forward. 

And so where would you go with that in myeloma? Well, some of the other talks [discussed] the early precursor stages of myeloma. And of course, if you had a benign, well-tolerated treatment that you could give to smoldering myeloma or MGUS, then you could intervene early and improve the survival of patients and really prevent the transition to cancer at all. 

So, we look forward to a future of cancer prevention rather than cancer treatment. That's really where I think we should go in the future. Thank you very much for listening.

Source:

Morgan G. Microenvironment and Clonal Diversity in Myeloma. Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-21, 2023. New York, NY