Patient-Reported Outcomes, Quality of Life for Luspatercept Versus Epoetin Alfa in MDS

A roundtable discussion, moderated by Hana Safah, MD, of the Tulane University School of Medicine, focused on the latest data in myelodysplastic syndromes presented at the 65th ASH Annual Meeting & Exposition. Dr. Safah was joined by Jamile Shammo, MD; Andrew Brunner, MD; and Tiffany Tanaka, MD.

In the next segment of the roundtable series, the panel discussed a study that assessed quality of life and patient-reported outcomes in patients receiving luspatercept for MDS.

Watch the next segment in this series.

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Dr. Safah: You spoke of quality of life, so I’m going to have you speak of the abstract that looked at patient-reported outcomes, PROs, of luspatercept versus erythropoietin. Can you shed some light on those data?

Dr. Brunner: Absolutely. I think that when we talk about symptomatic improvement in patients with MDS [myelodysplastic syndromes], we’re hinting at this idea that we’re improving their quality of life. I guess in some ways if you have to come and spend half a day with me in clinic and then all of a sudden don’t, maybe that is an improvement in your quality of life. But it’s been very difficult to consistently show benefits in patient-reported outcomes in MDS trials. Conceptually, especially in low-risk trials, we should be aiming for that because we are intending to give someone a new drug and remove transfusion needs with the overall goal that their quality of life is improved. In this study, this used the COMMANDS patient cohort, they collected patient-reported outcomes through the first 25 weeks of treatment, and they did it both in the erythropoietin arm as well as in the luspatercept arm.

What they showed is that really the luspatercept arm did better in all the domains that they assessed. Particularly in shortness of breath or dyspnea, luspatercept improved, and then the overall score, there’s an improvement over the duration of the trial. I think that’s an encouraging sign that that intervention in the frontline is also translating into improvement in patient-reported outcomes. There’s a lot of caveats to patient-reported outcomes. If you take it before the transfusion or after the transfusion, you might have a very different response. If you take it when people are hospitalized … there’s a lot of things that can influence these kinds of scores, but I think it’s really commendable that they’re trying to get to the most meaningful thing. Are patients feeling better when we’re treating them and is there a difference between the types of treatments that we use?

I think that this adds to the frontline data and adds to the COMMANDS study. I will say it’s interesting because this data is a little different from the MEDALIST data. They did PROs during MEDALIST, which was in the second line, later phase of disease, and they saw less obvious differences between groups. This really does suggest that maybe timing of treatment initiation and how you’re influencing how transfusion-dependent patients are, those can also play into PRO improvement. But I’m pretty encouraged by this data, and I think it’s really in line with the idea that we can intervene early with luspatercept in these patients.

Dr. Shammo: I like what you said about the differences between the two trials because indeed in the MEDALIST, the differences weren’t that robust and yet the comparator arm was a placebo. Here you have a comparator that’s active therapy. It’s difficult to compare trial to trial. But it definitely is encouraging. I wonder how much of the improvement in PROs is because you don’t have to go to the center every week.

Dr. Safah: That’s very important. Honestly, I say it’s improvement in the quality of life of the patient as well as the caregiver because they have to also come with the patient and that can add [up]. But through the discussion we are seeing some change in the way we look at MDS. Now we’re talking about genetic mutations. The importance of the mutation in response because of those. We’re doing molecular studies on these patients and we’re having a precise classification or categorization. Then we started talking about quality of life, which is something that we never spoke [about]. We just transfuse, give them erythropoietin and then, “Come back, see me later.” Now we’re saying, “Well, maybe we should do better.” We’re listening to them first, we’re collecting data from them, and then maybe that should become part of the trial, an endpoint that we study on a trial.

I think that’s how I see things. It becomes very important too. Are we improving quality of life just because we’re making the hemoglobin better or is it something that we’re doing with the inflammation of the disease set? It’s not just them not coming to receive red blood cells but is it changing the nature of the disease and what we know about the inflammatory mechanism that is associated—they might be feeling sick from that and that inflammation that can be affecting other organs.