How can stratifying smoldering multiple myeloma patients be used in making treatment decisions?

How can stratifying smoldering multiple myeloma patients be used in making treatment decisions?

It's very important to stratify smoldering myeloma because we don't want to under treat people, but we don't want to over treat people as well. And we know and probably every person who takes care of people with myeloma has seen that person who's had very high protein levels for 20 years. I certainly have. And they've been fine. They have not gone on to get myeloma. Now, of course, we would love to figure out why that is. But then we also can see people who have come in maybe diagnosed with smoldering myeloma at another facility six months ago, and now they have myeloma. So those people we would love to have an opportunity to say before you get a bone fracture, before you get kidney problems, we would like to figure out who you are. Jump in and perhaps offer you appropriate treatment at that point to prevent you ever from getting myeloma. And that's really the goal here to not over treat, but also not under treat. Smoldering myeloma is such a heterogeneous disease. I can have ten patients diagnosed with smoldering myeloma because they have 10% cancer cells in their bone marrow. And yet some of them will behave more like an MGUS and may never go on to progressive myeloma. And some of them may behave more like multiple myeloma and will go on to progress very rapidly in the next couple of years. And I think the later part, the ones who will progress, are more like a stage one, stage two cancer. You do want to think those patients have the cancer. They have already the clonal mutations. They look like myeloma, but have not met the metastatic myeloma. So they're like an early breast cancer already developed. This is not TCIS. This is already well-developed cancer, just not metastatic. Those are the patients that we should likely treat and treat aggressively because you don't want to develop resistance and selection. Then there are the patients who are more MGUS-like and those you need to stratify them better because some of them may never go on to progressive myeloma and you should not be treating them unless we have, of course, things like vaccines and other methods that are easy, simple, less toxic, that could potentially eradicate the disease. But there's always the benefit and risk from everything. So think about what is the long-term evidence that they will go on to develop myeloma. Can I prevent it and can I use something that would not cause harm by preventing it? I see many patients who are in their thirties with a high-risk MGUS or a low-risk smoldering myeloma. I know that many of those may go on to develop myeloma when they're age 60, and we should think about that too, what is their longevity and what are the chances of developing multiple myeloma? So we have to put all of that together. And as we develop better immunotherapy, whether it's the CAR-Ts, immunotherapy of bispecific, trispecifics, or even vaccines. So using all our material to really harness the immune system and kill it early, we could make a difference in completely eradicating multiple myeloma before it happens.