Benefits of Early MGUS Screening: iStopMM Study Results | Sæmundur Rögnvaldsson, MD, PhD | ASH 2023

Hi, my name is Simon de Rokholtzon. I am a physician and postdoctoral researcher at the University of Iceland. And I'm part of the study group doing the Iceland Screen Streets or Prevent Multiple Myeloma Study. So I'm here at ASH this year presenting two abstracts of the many I-STOP-MM abstracts this year, including abstracts on the current headline results of the I-STOP-MM study. So to sort of tell you a little bit about the I-STOP-MM study, multiple myeloma is a disease that often shows up with severe end organ disease. People show up with kidney failure, fractures, and often severe bone disease. But in reality, it develops over many years, even decades, from precursors, MGUS or monoclonal gummopathy of undetermined significance and smoldering myeloma. And recently, we have seen that if we treat people earlier at an asymptomatic stage, we can improve their outcomes. However, less than 10% of myeloma cases are actually diagnosed at this asymptomatic stage. So we're asking the question, can we apply population-based screening, cancer screening, to improve upon that and provide early detection and early treatment in myeloma and hopefully improve outcomes? So we started in 2016 in Iceland and invited everyone born in 1975 and before. That's around 150,000 people. It's a small country. And around 81,000 people provided informed consent for the study. And then next, we collected blood samples alongside other blood sampling in the Icelandic healthcare system. We have now screened 75,422, which is just over half the total population of Iceland in this age group. We have identified 3,600, thereabout, individuals who have MGUS, this precursor, this asymptomatic precursor. And these people are randomized to three arms. Arm one, which is the control arm of the study, similar to a placebo arm in a drug trial, is not notified and continues care like they were never screened. Arms two and three are called in for further clinical assessment of a little bit differing intensity. It was the most intense follow-up in arm three with bone marrows for everyone and imaging and so on. So we've now been doing this follow-up for a few years and the results which I'm presenting here at ASS this year seem to show that this screening actually leads to earlier diagnosis of myeloma about one year earlier. And the interesting part and the important part is that we're not over diagnosing myeloma. We're just diagnosing it earlier, about one year earlier. And at that time point, we see that the myeloma patients that we diagnose through the screening have fewer or less end-organ disease and they present in a different manner. You know how some myeloma patients present with very severe disease and they require dialysis or they have fractures requiring admission, but we decrease the likelihood of that type of presentation by around or a little bit more than 75 percent. So what we find is that through screening we are really changing the face of myeloma and how we're seeing it in the clinic. But there are of course some important caveats which are that we need longer term follow-up to see whether this translates to improved outcomes long term. Does this actually prolong survival or are we just adding a year of treatment to their lives? And that's a very important thing we need to look into going forward. And also screening is a big public health intervention and we need to be sure that it's worth it from a resource utilization standpoint and an economic standpoint, both for individuals and our healthcare systems before we can recommend screening. But the results seem to be promising and seem to show that screening really changes how we see myeloma in the clinic. And that's the headline results of the study to date.