IMS 2026 | Predicting cure in MM: identifying an ultra-low-risk subgroup who may benefit from stopping therapy

I think that part of what’s exciting about this IMS in general is that the development of this new universal cure definition of looking at patients who are sustained MRD negative, imaging negative remission lasting for at least five years off therapy, and how can we get more and more patients to that time point, and I think what’s really interesting about it is the way I see it, is that we really want to try to figure out who are the patients that we can stop therapy in early, who are these potential cure candidates that might benefit from stopping therapy from that longer treatment-free interval and potentially even be cured after time. So I think we wanted to look at our patients to try to understand, was there a subgroup of people who perform really, really well even off therapy? So what we did is we looked at patients who really did not have any high-risk features, so patients who were ISS stage 1 to 2, were genomic standard risk by the updated consensus classification, and had the best MRD available we have. So their MRD was confirmed at being negative at least 10 to the minus 6 by NGS. And we showed that for those patients, once they reached two years of sustained MRD negativity, or 24 months, their subsequent relapse risk, either on or off therapy, was extremely low. And at the same time, the minority of patients who did relapse, and we found it was just about 3% of patients who relapsed at five years off therapy for that group, had a very indolent relapse with very sensitive disease. So that, to us, this was retrospective non-randomized data, but to us, it centered this idea that that type of subgroup might really benefit from being able to stop treatment, potentially even getting towards cure. So I think we’re very excited. And again, everybody’s going to have a different experience and particularly looking for individual patients and prospective randomized data, you know, we’ll continue to address these questions more and more. But I think particularly this idea of can we find a very low-risk subgroup that actually really benefits from early treatment cessation, I think was really important to us. And I think that trying to combine a couple of these low-risk features with patients who have already had at least two to three years of sustained MRD negativity, it might be a really good place to start as patients who really benefit from stopping therapy. I think both in our data and also as part of the cure definition that they announced at this conference, having the best degree of MRD depth or MRD at 10 to the minus 6 by NGS is a really important way to establish absence of disease or at least absence of disease to the best way that we can detect it. I think it is true that people who don’t have access to deeper MRD at 10 to the minus 6, that’s okay. And I think that there is still a lot of really important data that was being presented both at this conference and has been shown previously that lower-risk patients can still benefit from that treatment-free interval of stopping therapy. So I think that even if those patients at centers that don’t have 10 to the minus 6 can’t officially meet the definition of formal cure, it doesn’t take away from the fact that a lot of those patients can have really exceptionally good outcomes either on or potentially off therapy. And it might, I think, start using the available risk tools that you have within the context of the best MRD testing that you have and really thinking carefully about whether my patients are going to benefit from continuous treatment or whether they can potentially stop therapy, I think is the operative question regardless of your MRD test.

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