Luspatercept Correlated with Clinical Benefit in Patients with Lower-risk MDS

Amer Zeidan, MBBS, MHS, Associate Professor of Medicine at Yale University and Interim Chief of Hematologic Malignancy Division in Yale Cancer Center, reflects on the COMMANDS study, a randomized, phase III trial that compared luspatercept with epoetin alfa (EA) in patients with myelodysplastic syndromes (MDS).

At the 2023 American Society of Hematology Annual Meeting and Exposition, Dr. Zeidan and colleagues will give an update focusing on the translational work in which analyses were conducted from the blood and bone marrow samples obtained during the COMMANDS trial.

Dr. Zeidan highlighted important messages from the study.

“The first message is initially, the thinking that luspatercept works mostly on late-stage erythropoiesis, while [erythropoiesis-stimulating agent (ESA)] has worked mostly on early erythropoiesis. But what the work actually showed is that luspatercept works on relieving the maturation defect not only at late erythropoiesis, but also on moderate and initial phases of erythropoiesis,” he said.

Additionally, Dr. Zeidan noted that luspatercept has shown to reduce inflammation, which is a major component in patients with lower-risk MDS. It also modulates the transforming growth factor pathway expressed genes, which mediates the reduction in inflammation and is correlated with clinical benefit.

“Our translational data can suggest mechanisms for which the clinical benefits that are seen with luspatercept are mediated,” Dr. Zeidan concluded.