ASH 2021 | First results of PROMISE: MGUS screening in a high-risk population

Yeah, we’re very excited. And it’s actually one of the best of ASH press releases this year. So, we wanted to understand better what’s the prevalence of multiple myeloma or developing monoclonal gammopathy in people who are at risk. So we know that the general white population, the risk is about, or the prevalence is about 3%, which Dr. Kyle has shown us for many years. And indeed the iSTOP study is showing us very similar numbers. However, what we wanted to see is, what is the risk of black Americans and people who have a first degree family member with blood cancer, because we’ve known that these are the people who are at risk, who have a much higher chance or prevalence of developing monoclonal gammopathy. So we started the PROMISE study a few years ago, and we added to it a cohort from the Mass General Brigham. So this is about 125,000 people who have been giving their samples whenever they go get their primary care physician, blood sample or any others.

Most of us, as physicians and people who work in the staff of Mass Gen in Brigham, give our samples. So it’s basically in the New England area. And the nice thing is that it has 20% of the people are diverse, African-Americans, Hispanics. Now you can start asking the question of diverse population. And we added those numbers together, and we have 7,662 samples of those patients. We screened it with the mass spectrometry from binding site, and we used for the first time their new algorithm, their AI algorithm, that can give you quantitative mass spectrometry. So, so far, Mass Fix has been a wonderful method done by Mayo Clinic, but it doesn’t give you quantitative numbers. So now we have the ability to see what is that monoclonal gammopathy below the levels that we didn’t detect before. And to our surprise, we found a very high number. The prevalence was very high of all monoclonal gammopathies.

So if I break it down, 3% is what you expect in the normal general white population. 6% is what we found if you just do the typical serum protein electrophoresis, so the standard of care. Again, because we know that we doubled the number by looking at a high risk population, 13% was what we found at numbers that are almost equivalent of what you would find by SPEP, but you’re finding it by mass spectrometry. So again, we doubled it again, and we know that mass spectrometry is much more sensitive than SPEP. But what we found is below that. There was another 23%. So a total of 40% of people are walking around with monoclonal gammopathies. And most interestingly, many of those that are below that MGUS level, what we usually detect, we wanted to give them a different name that’s not MGUS, because we don’t want to say 40% of us are walking around with MGUS. So we gave it a name called monoclonal gammopathy of indeterminate potential or MGIP, which is like CHIP. And as we know, CHIP, clonal hematopoiesis of indeterminate potential is another early, early precursor condition.

So we’re trying to say, this is something that we still don’t know what it means. It may go on to malignancy in the future. It may not. But let’s understand what’s going on with abnormal monoclonal proteins in many of those high risk individuals, and what is the long term outcome. Now, the interesting part is, we do have long term outcome from the MGB cohort, because they’ve been followed for 10 years, and with a median of 4.5 years of follow up on the samples that we have, we found that indeed there was an overall survival difference that people who have this MS MGUS, mass spectrometry MGUS, as well as high MGIP, the high level of MGIP that’s almost MGUS, had the worst overall survival. Not all of them are dying from myeloma, which we know, and actually, this is very similar to what Dr. Kyle has shown us.

They die from other things, cardiovascular disease and other comorbidities, but they are having a worse survival. And that’s interesting, because now, we’re trying to understand why having a monoclonal gammopathy makes you have this immune fitness problem. You have an immune dysregulation, and is that leading to other hematological malignancies, to inflammation and myocardial infarctions, to autoimmune diseases? There’s so much to be understood in the population. And then later on, we can ask the question of, what is the clinical significance? How can we prevent it? This hopefully will open the door for so many biological questions and so many clinical questions, especially for our at risk people.

And I just want to highlight that this is the largest African-American cohort that has been screened to date, and we are so excited to try and expand that to really close the gap of early detection, early interception, especially for people who are at risk.