EHA 2026 | Could luspatercept modify disease in lower-risk myelodysplastic syndromes?

We are certainly talking more than anemia response and symptomatic control. With the data that are currently being read out in the frontline setting with the COMMANDS trial, there is a trend towards survival benefit. And that’s a trend only because the trial was not designed or large enough to show a survival benefit. That was not the primary endpoint, and yet there was a trend towards survival benefit. I’m sure that if the trial was bigger, you would actually see that p-value also move in the direction of actual statistically significant benefit. The lower-risk MDS, we didn’t have agents like this before, so we’ve always been talking about anemia improvement, but as we are seeing these data, lower-risk MDS has, you know, these questions are now being raised, can we modify the disease? There’s lots of data with luspatercept that support that mechanism, right? The erythrocyte stimulation is just part of it, but it also has anti-inflammatory effects. It has trilineage effect where you can have a platelet and neutrophil response as well, which is important in terms of infection and bleeding, and the cardiovascular modification. I mean, patients who are on the COMMANDS study, when they were responding to luspatercept, there was a reduction in NT-proBNP, which is a predictive marker for future cardiovascular risk and mortality. So patients are having better cardiovascular biomarkers on those luspatercept. There was a reduction in hepcidin. Again, it’s an inflammatory sort of, it’s a marker of higher inflammation in the body. So as we modify these predictive biomarkers that tell us about the future risk of mortality, we are doing two different things, right? We’re not only trying to improve survival by modifying their other comorbidities like cardiovascular disease, but at the same time also as this luspatercept moves more and more in the frontline setting and the potential, and even at the point where they’re NTD or non-transfusion dependent, that we have the ELEMENT study, which is ongoing in that as well. We’re using those luspatercept earlier in stages where the anti-inflammatory effect might actually be important in those modifications. So we certainly are moving in a direction of can we actually modify the disease and make our patients live longer rather than, you know, we’re just doing it for the anemia.

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