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ASH 2025 | Is high-risk smoldering myeloma a misnomer – do these patients already have myeloma?
Francesco Maura, MD, Memorial Sloan Kettering Cancer Center, New York, NY, discusses whether high-risk smoldering multiple myeloma (SMM) is a biological misnomer and whether, based on genomic data, these individuals already have active myeloma. Dr Maura highlights that 10% of SMM cases show no evidence of malignant transformation and are termed genomic monoclonal gammopathy of undetermined significance (MGUS). While the remaining patients have evidence of neoplastic transformation, Dr Maura notes that this does not necessarily mean they will develop organ damage. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
According to our data, which is, despite this, the largest cohort of smoldering profiled by genomics is still small compared to, for example, what we know about newly diagnosed myeloma from a statistical power standpoint. So what we know is that 10% of smoldering are kind of benign or don’t have evidence of malignant transformation. We don’t like the word benign because we cannot exclude that there is some neoplastic clone somewhere else, not in the marrow, maybe in the ribs or in the sternum and not in the iliac spine where we do the bone marrow...
According to our data, which is, despite this, the largest cohort of smoldering profiled by genomics is still small compared to, for example, what we know about newly diagnosed myeloma from a statistical power standpoint. So what we know is that 10% of smoldering are kind of benign or don’t have evidence of malignant transformation. We don’t like the word benign because we cannot exclude that there is some neoplastic clone somewhere else, not in the marrow, maybe in the ribs or in the sternum and not in the iliac spine where we do the bone marrow. So we use no evidence of malignant transformation and we call them genomic MGUS.
All the other patients have evidence of malignant transformation meaning they are already neoplastic, but that doesn’t mean you develop organ damage. That’s because as every tissue in our body ages and by aging, certain tumor cells or neoplastic cells start to emerge. Most of them are killed by the immune system, most likely. Others consolidate over time. Ninety percent of men above age 80 have prostate cancer, but very few of them have metastasis and require therapy or die from prostate cancer compared to the global population. So the same with MGUS and smoldering. The fact that you have a neoplastic transformation in the marrow doesn’t mean you will get the myeloma. We don’t live 200 years, so we will probably… most of these patients will die from something else.
Now, patients with high disease burden and genomic complexity or evidence of clonal transformation, those are patients that we need to monitor more actively and consider for interventional trials. Patients with both high-risk genomics and prognostic score like IMWG, those are patients that may require more thinking from the community and see if we want to consider them myeloma so we can treat them properly.
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