COMy 2026 | Insights into functional high-risk myeloma and how to adapt treatment for these patients

Functional high-risk in myeloma is what we normally call when a patient experiences an early relapse, and that early relapse is not really explained by the diagnostics that we do up front. So, we have, of course, always noticed that with one-size-fits-all treatments, which is currently still the main treatment that we do, about a quarter of patients unfortunately have not a lasting response, but the disease comes back. Despite initial, often even deep responses, we see relapses within the first 24 months of therapy. Now, a lot of that is a problem of a one-size-fits-all treatment, but a lot of it is also a problem of diagnostics. I think myeloma, of course, understandably had more focus on using new drugs because the drugs that we had didn’t use to work very well for everyone. Now that we’re entering an era where nearly everyone responds, we suddenly see that we also have a need for diagnostics. Now, we did a recent investigation into patients that are relapsing with the one-size-fits-all treatment, and we found that with the current genetic diagnostics, we do indeed miss about 40% of these early relapses, which we would then call functional high risk. But if we use better diagnostics, we can actually reduce that number quite a lot. We can actually reduce the number of less than 20% unexplained relapses. Now, why is that important? The question is then, if you know earlier whether a patient has a risk of an early relapse, can you change their outcome if you change their treatment? And actually, for many patients, we can. This is just research that we are publishing at the moment in a trial that we, for example, ran, but others have done very similar research called the OPTIMA MAC-9 trial. We did exactly that. We diagnosed upfront and then changed to first-line treatment. And for the majority of those patients that we can identify as high risk, we can actually improve the outcome if we change to treatment upfront. For those where we do not do that, there’s now interesting data, even from later CAR T-cell treatments, that the treatment effect is not quite so good once the early relapse has happened. And that’s because the disease tends to acquire new mutations when the disease relapses. So actually the subsequent treatment is always more difficult than the first-line treatment.

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