Evolving MDS Treatment Options and the MEDALIST Trial

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 discusses the evolution of MDS therapy and how the MEDALIST trial set the stage for luspatercept as a treatment option.

Watch the next segment in this series.

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Dr. Safah: Today what we’re going to do is we’re going to go over what is available for our patients and what is coming up as new treatments and what is in the future that’s going to become available for those patients. Let’s start with the question of what is available for us as physicians and for our patients to take care of them. Dr. Brunner?

Dr. Brunner: Yeah, it’s a great question. We have known about patients who will have lower-risk MDS [myelodysplastic syndromes] and been able to classify them for many years and essentially find this group of people who will coexist with their cancer for many years but will have consequences of it from their anemia largely. Historically, we would support them. We would use red blood cell transfusions, and that can be at various intervals. Some patients may only need intermittent red cell transfusions every few months. Some will become heavily transfusion-dependent, needing several units of blood every two weeks or even weekly.

One of our options that we have used therapeutically for a long time is trying to boost red cell production using growth factors. There are a number of erythropoietin-stimulating agents. There’s epoetin alfa; there are multiple versions of that. There’s a longer-acting darbepoetin. We would use these at very high doses trying to extract whatever function out of the bone marrow that we could. For some patients who have a loss of chromosome 5q, they would be very responsive to a pill—lenalidomide. For those patients, almost 80% of them will have a response to the use of lenalidomide to improve their anemia.

But for many years, by and large, that was all we had. Within the last five to 10 years, we have discovered a new drug, luspatercept, and that has become approved initially in the second-line setting, and now has been explored in the frontline setting of using luspatercept, particularly for patients whose MDS harbors ring sideroblasts. I think what we’re seeing in the field is a growing repertoire of options for patients with predominantly anemia and ways to manage that anemia as they coexist with it over time.

Dr. Safah: You have alluded to the MEDALIST trial. Dr. Tanaka, do you want to share with us the MEDALIST trial and the data that came out of there?

Dr. Tanaka: As mentioned, luspatercept was studied. This was back in 2020 where luspatercept was compared to placebo in a randomized trial. They specifically focused on MDS with ring sideroblasts or MDS-RS, and they found that luspatercept, not surprisingly, was superior to placebo. It had nearly a 40% transfusion-independence rate. That really is beneficial to these patients. It lowers their burden of time spent getting transfusions, the many hours, and then the long-term health effects such as a transfusion-related iron overload. It was an exciting trial, and it helped set up perhaps the next trial that we’ll focus on after this. One difference is that we no longer really say MDS-RS. The WHO [World Health Organization] in 2022 said, “Let’s make it more homogeneous. Let’s call it MDS with SF3B1 mutations.” We don’t really think of it as MDS-RS anymore.

Dr. Safah: Yeah, and that’s really helpful because the MDS and the International Consensus Classification, the MDS SF3B1 presented as a homogeneous group that has a lot of, they share the same presentations phenotype, different from the way we used to look at MDS-RS positive mutated or wild type. That is very true.