Biomarker Analysis on Inflammatory Effect for Luspatercept Versus Epoetin Alfa in Patients with 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, Dr. Tanaka outlines a biomarker study that observed reduced inflammation in patients with MDS treated with luspatercept.

Watch the next segment in this series.

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Dr. Safah: This is what I’m going to have Tiffany talk to us about—luspatercept modulating inflammatory reaction. I think that’s how we’re evolving in understanding the disease.

Dr. Tanaka: I thought this was a really satisfying abstract. It’s always nice to see some biologic or biomarker study that really translates clinically. This abstract looked at the erythroid precursors as well as the inflammatory molecule pathways and compared the luspatercept to the erythropoietin arms. What they found is that the erythroid precursors and the reticulocyte count, that actually was higher in the luspatercept arm when compared to the erythropoietin arm, and this was durable too, it was up to that 48 week mark.

Clinically, that makes a lot of sense. You would expect that the luspatercept drug would actually prompt more effective erythropoiesis. Then what you mentioned too was the inflammation was turned down. This was done by RNA sequencing, and they found that a lot of the pathways we expect interferon, IL-1B, IL-10, etc., those were all down regulated in the luspatercept arm compared to the erythropoietin arm. Just as you mentioned, maybe that really makes people feel better too, reduction of the inflammation, and that changes the bone marrow microenvironment and helps promote normal red blood cell maturation.

Dr. Safah: That’s perfect. The interesting part to me in that abstract was looking at the BMP, that is to me, because we know patients with CHIP [clonal hematopoiesis of indeterminate potential], who might have the same mutations that we see with MDS end up with more cardiovascular disease. Maybe there is some connection there and having decrease in the BNP in these patients, is it just because we decreased the transfusion burden or are we doing something different in these patients with certain mutations? I’m loving this era because now it’s not just MDS; it’s something else we’re doing to the disease. Thank you for sharing that with me.

When we look at all these abstract, as I said, we’re hearing sound bites that we’re not there before—quality of life. We’re hoping that it becomes an endpoint that is studied in clinical trial because it’s very important to these patients to know is this just what we’re doing or is it something to do with the biology of the disease and how they’re feeling from that?