What is the definition of high risk smoldering multiple myeloma?
Is high risk smoldering multiple myeloma the same as high risk multiple myeloma?
We define high risk as 50% risk of transforming to active myeloma.
And those patients are the ones that we know are likely to benefit from therapy.
So the difference is actually vast.
So smoldering myeloma is myeloma that is diagnosed as multiple myeloma.
But it seems to be quiescent.
It doesn't seem to be affecting you in any adverse ways.
You may not, you don't have any symptoms from it.
And so the question becomes, is that just the myeloma waiting to explode and become an active myeloma, or is it something that you may live for many, many years and never become an issue?
Active myeloma, of course, is when it's active, it's hurting your body, and you don't want to leave it alone because it will continue to hurt your body and eventually you can die from it.
So requires immediate attention.
So when we talk about high risk in active myeloma, we talk about the risk, in terms of the likelihood that you would respond to therapies, how like how long you're likely to stay in remission and perhaps how long you may live with this disease that is high risk myeloma.
And we might do some treatments differently depending on those risk factors.
When we talk about high risk smoldering myeloma, but looking at certain parameters, certain clues that might tell us that perhaps this patient with smoldering myeloma is much more likely to become active myeloma than stay in that smoldering phase where they may not need any therapy.
Right now, the way we identify a high risk, a smoldering multiple myeloma is really based on the 20/20/2 which is more than 20% plasma cells in the bone marrow.
The free light chain ratio of involve over and involve is more than 20 or the monoclonal protein more than two gram per deciliter.
And if you have two of these, you are considered high risk.
And the risk in smoldering myeloma is risk of progression.
So what is the risk of progression?
Used to be 10% per year.
So that means 50% of the patient will progress in five years.
But the high risk group the risk of progression at two years is about 54%.
So these are the patients that there are a lot of investigation ongoing try to address that group.
Whether we should use a cure based regimen like the in the Ascent trial, or should we, use a different approach, to it?
the high risk myeloma is really based on the cytogenetics.
So if you have, you know, amplification of 1q, translocation 14;16 or, tp53, 17p deletion, those are considered high risk.
It's intriguing that some of the trials suggest that if you have those cytogenetics, abnormality and high risk smoldering myeloma, they don't have the same impact.
But obviously we need to collect more data.
We need to have more patients into a database that will allow us to really understand that better.
HealthTree • July 12, 2025
