ASH 2023 | iStopMM: the psychological effects of MGUS screening and changes to clinical presentation of myeloma

So, I’m presenting the current headline results of the iStopMM study at this year’s ASH. So the iStopMM study, or the Iceland Screens, Treats, or Prevents Multiple Myeloma study, is a large population-based screening study ongoing in Iceland with a follow-up randomized trial of follow-up strategies, in order to look at the benefits and the harms of screening for MGUS and early myeloma. 

So, the problem we’re trying to solve is that less than 10% of myeloma is diagnosed at an asymptomatic early stage, but we know that if we diagnose people early and treat them early, outcomes are probably better, or they appear to be better. So, we invited everyone in Iceland 40 years and older to participate, and we have now screened just over half the total population in this age group, 75,422 people that were now screened. And we have identified 3600 individuals with new MGUS, which were then randomized to three study arms. Arm one is essentially the control arm, similar to a drug trial, a placebo arm, if you will, where people are not notified and continue care as though they were never screened. But then we have arm two and three, where we call people in for clinical evaluation and follow-up. 

So, the results I’m presenting this year are around how this affects the presentation and the outcomes of these individuals, sort of in the medium term or early, actually. So what we see is that when we do screening, we diagnose people with myeloma and related disorders about one year earlier. And what’s also important is that we appear not to be overdiagnosing myeloma and related disorders, we’re just diagnosing them early, the people in the control arm, they catch up later on. And this is also illustrated in how these myeloma patients show up in the clinic. They have less end-organ damage and are less symptomatic at the time of diagnosis, and importantly, their mode of presentation is also different. We have about a 75% reduction in acute presentation of myeloma, which is something that we as clinicians know very well: myeloma patients who show up with severe renal failure or severe bone disease necessitating admission, that’s associated with worse outcomes. So, we find that really the clinical presentation is different when we diagnose it this early. 

So the third thing that we looked at here in this data that I’m presenting this year, is the psychological effects of being diagnosed with MGUS. So that’s one of our worries, is that when you screen a whole population, you tell a lot of people that they have early cancer or precursor, that will lead to a decrease in their quality of life. So we looked at anxiety and depression and satisfaction with life through questionnaires both at baseline and then repeatedly over time. And actually, to our surprise, we see that intervention when we look at the scores, the results actually seem to favor those who know about their MGUS, so those who are in the intervention arms. That’s not to say that screening for MGUS is a mental health intervention or anything like that, the difference isn’t clinically significant, but the key takeaway from that is that we’re not increasing their anxiety or depression, at least by the measures that we’re using to measure it in this study to date. But we’re working on analyzing that a little bit more closely in order to understand that better. 

So taken together, the findings are that screening leads to early, not overdiagnosis of myeloma and related disease; screening changes the clinical presentation of myeloma, but it does not lead to anxiety, depression, or increased dissatisfaction with life. There are important caveats. We don’t know whether this translates into improved outcomes, like survival and more long-term outcomes, and we will need more time for that and that’s critical if we want to start screening. And the second sort of caveat is that, we also have to think, is it is it worth it? We’re screening thousands of people, and if we start screening, we will screen millions, and this will, of course, strain healthcare systems, both from a resource utilization standpoint and also an economical standpoint. So we need more data on that. But we also have to remember that we have a structured follow-up and give clear information to our participants about their diagnosis and the follow-up is free, which is important when we think about the psychiatric outcomes. But even so, we really can say now, with the current data from iStopMM, that screening really changes the face of multiple myeloma, and that’s sort of the current findings of the iStopMM study.