High-risk myeloma represents 15 to 20 percent of all multiple myeloma patients and is defined by specific genetic abnormalities and other factors. In this Health Tree University lesson, we will learn the definition of high-risk myeloma and functional high-risk myeloma. What is high-risk myeloma? If you're considered to be high-risk disease or you're told that your myeloma is high-risk disease, basically what it's telling you is that the myeloma that you have is going to be more likely to want to come back sooner. So if you respond to treatment and you achieve a good control of your disease, it's going to probably come back sooner than somebody who does not have high-risk disease. Why is that important? That's important because high-risk disease is harder to treat. Sometimes it's harder to achieve a good remission in high-risk disease patients and it's hard to control. And then if it is controlled or if we manage to do debulking of the disease, it's going to want to come back sooner rather than later. And that translates to having to need more chemotherapy to try to control the disease better. And it also means you're going to have a less probability of surviving myeloma than somebody who's standard risk. Now having said that, if somebody is established to have high-risk disease or has been told that they have high-risk disease based on their cytogenetics or based on the staging or other criteria that defines them as high-risk disease, it doesn't necessarily mean that that's it, that you are going to behave like high-risk and your disease is going to be hard to control and that your outcome is not going to be that good. You're not doomed. It's just a predictor. So we're not gods and we can't see the future. These tools that we use to define somebody as being high-risk or standard risk are just guides to help us see what the odds are in the future, but it doesn't necessarily mean that you're going to follow that criteria. And I see in clinic people who have high-risk disease with 17-P deletion that stays in remission for years. And we have other patients in clinic who don't even have any mutations and they are having a hard time to achieve a remission with conventional chemotherapy. So I want to emphasize that because it's important to keep this in mind, but it doesn't necessarily define what your future is going to be like. It's just a predictor of what we could possibly expect based on what we've seen with prior patients or prior clinical trials that we have done. When we look at a group of patients, we know that their response to treatment, their time in a remission and their overall survival will vary between those patients. And so we've tended to call the group of patients who unfortunately don't respond to therapy all have a short survival as having high-risk disease. Now it's always difficult to know how many patients should fall into that group, but traditionally it's been about 20% of patients. So those patients who we think might have the worst outcome from therapy we call high-risk. Functional high-risk is something that you don't predict at the time of diagnosis because these other staging systems that I mentioned, this is a stage that we assign right at diagnosis based on testing done on the patient and the patient's bone marrow right then. Functional high-risk myeloma refers to patients who, despite initially appearing to have standard risk disease, experience early relapse. Functional high-risk is something you find out about after. It's a patient who you wouldn't have guessed would be high-risk but has either a primary resistance to therapy. Their disease either resists therapy right out of the gate, that's not as common, or they relapse earlier than you would expect, way shorter than average. And when that happens going forward, functionally they are higher risk. They've told you, or their myeloma has told you, you know, I'm going to misbehave, right? And so going forward, those patients probably should be treated like high-risk patients too and I think there's a lot of effort at understanding why some patients who don't have the traditional obvious risk factors for rapid progression still end up being rapid progressors.
HealthTree • August 22, 2025
