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IMS 2025 | The challenges of managing high-risk myeloma and the need to optimize outcomes
Gareth Morgan, MD, PhD, FRCP, FRCPath, NYU Langone Health, New York City, NY, discusses the challenges of managing high-risk myeloma and the need to optimize outcomes for these patients. He emphasizes that although progress has been made in improving outcomes over the past decade, high-risk myeloma continues to present a major clinical challenge. Prof. Morgan highlights recent updates in the definition of high-risk disease and stresses the importance of ensuring patients gain access to novel therapies that can further improve outcomes. This interview took place at the 22nd International Myeloma Society (IMS) Annual Meeting in Toronto, Canada.
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Transcript
So this has been a great time for high-risk myeloma in a way. People are realizing that it constitutes a significant clinical problem and we’re really trying to address it so that we can improve outcomes. So the fundamental problem has been we’ve made some inroads into improving outcomes in the last decade. But basically, it’s remained a very, very poor outcome, clinical state in myeloma with poor responses, poor disease-free survival, and rapidly people are dying...
So this has been a great time for high-risk myeloma in a way. People are realizing that it constitutes a significant clinical problem and we’re really trying to address it so that we can improve outcomes. So the fundamental problem has been we’ve made some inroads into improving outcomes in the last decade. But basically, it’s remained a very, very poor outcome, clinical state in myeloma with poor responses, poor disease-free survival, and rapidly people are dying. So we need to pay attention to this clinical disease. The challenges are recognizing it. And so when you see a patient that’s newly diagnosed, how do you know if they’re going to be good prognosis myeloma or behave more aggressively? So we’ve changed the definitions recently. So now there’s a standard, simple definition of multiple myeloma based on lesion counting, really. So if you have just one high-risk lesion, that’s not high-risk anymore. If you have two high-risk lesions, well, that’s going to mean you go into a trial maybe directed specifically for high-risk disease. If you have three adverse lesions, then really, we really need to work hard for that group of patients. So basically, the adverse lesions are t(4;14) and t(14;16), which are the etiologic translocations. And then basically, it’s if you have that plus gain of chromosome 1 or amplification of chromosome 1 or loss of 17p. So it makes it really very easy to diagnose high risk now. So those molecular lesions plus a high beta-2 microglobulin really encapsulate the entire group. And so simple definition, focus on standardization of treatment and improving outcomes. And I think the really interesting thing is that the new T-cell engaging therapies like bispecifics and CAR-Ts, there is some evidence that patients treated with those entities, even if they have these adverse lesions, are doing better than you would expect. So really, we need to work out a way of getting those new treatments to people with the new definition to improve outcomes. So I think we have a clear way forward in this area.
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