What is MGUS?

What is MGUS?

Monoclonal gammopathy of undetermined significance, which is a big long name that first of all it is not of undetermined significance because we know of the term and significance for it. And I like to say the story that Robert Kyle, who I trained with at Mayo Clinic, coined the name. He's the one who first described that word. And it was because they found all of these monoclonal proteins in many people. And him and John Waldenström who described Waldenström macroglobulinemia, were debating whether this is a benign condition or not. And Bob Kydd said, well, I don't think it's benign. Maybe some of those patients would develop myeloma. So he wanted to make sure we don't call them benign gammopathy so that we know that those species may actually have an undetermined significance. Maybe they will go into myeloma. And he's the one who developed the whole Olmsted County study to follow patients for 50 years to make sure that we understand that rate of progression of 1% per year. So it's really special for me to have been trained by Bob Kydd and then now work on this area.

MGUS is the earliest stage, which is typically characterized as the patient having less than three grams per deciliter of an M spike and less than 10% plasma cells or cancer cells in the bone marrow.

Is MGUS considered cancer?

MGUS is considered a pre-cancerous condition, it has cancer cells. So it's very interesting. The cells themselves have a lot of changes that are very similar to myeloma, even the immune microenvironment of the bone marrow. Now we know that is also altered. It's already changing even in MGUS stage. But for some reason those cells have not been able to get to that next level of growing and proliferating and changing things to the point that they develop disease. So when you have a 1% chance of progression per year, that's very low, which means those cells need something else to happen so that they go to myeloma. That's something else. We don't know what it is. It could be a second hit mutation. It could be an immune change. You get some infection and that triggers the whole point. We don't have an understanding of why people go on to progress to myeloma.

What percentage of the general population has MGUS?

If we look in general and this was from Olmsted County, at age 50, 3% of the population has a risk of developing MGUS. Now, we know actually that African-Americans have a three times higher chance of developing MGUS and at a younger age, at age 40 or younger. And we know that first degree relatives of people—so sisters, brothers, mom, dad—have a three times higher chance of developing MGUS if they have a sibling or someone first degree relative. Now, if we look at the mass spectrometry, which is a new sense of test to look for monoclonal protein in Olmsted County, and this was just published, the number is 5% now, so it's even higher than the 3%. And in our own data, we're starting to see in the promise study the people who have high risk for developing myeloma. So the African-Americans or the first degree relatives, they're almost up to 13 and 15%. That's a huge number. And if that's true, maybe that would be one of the options for us to see less consider screening in the future for high risk population, because that's a big number of people who may actually have a monoclonal protein. And we're missing it out because we're not looking for it.

How long can I have MGUS?

I can have MGUS forever. I mean, never have a myeloma in the future. It's interesting. There are some MGUS that disappear on their own. So it could have been an infection, some autoimmune thing, and then it goes away. But these are rare. The most common ones are MGUS that are there forever, or they go on to develop smoldering myeloma, or they go on to develop myeloma or amyloidosis or Waldenström or CLL, or so many other things.