Luspatercept Shows Clinically Meaningful Improvement Over ESAs in MDS


Guillermo Garcia-Manero, MD, discusses the design and outcomes of the phase 3 COMMANDS trial in patients with low-risk myelodysplastic syndromes.

Guillermo Garcia-Manero, MD, professor, chief of the Section of Myelodysplastic Syndromes, deputy chair of Translational Research, and fellowship program director in the Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses the design and outcomes of the phase 3 COMMANDS trial (NCT03682536) in patients with low-risk myelodysplastic syndromes (MDS).

According to Garcia-Manero, the phase 3 double-blind MEDALIST trial (NCT02631070) led the way for the COMMANDS trial. Patients with very low–, low-, or intermediate-risk MDS, ring sideroblasts, and who required blood transfusions were randomly assigned on a 2:1 basis to luspatercept-aamt (Reblozyl) vs placebo.

In the open-label COMMANDS study, patients were randomly assigned 1:1 to receive luspatercept compared with the erythropoiesis-stimulating agent (ESA) epoetin alfa. Garcia-Manero noted that this trial did not require patients to have ring sideroblasts or SF3B1 mutations. In addition to statistically significant improvements in transfusion independence, duration of response and toxicity were favorable as well.


0:08 | The COMMANDS trial was based on a prior trial called the MEDALIST trial...MEDALIST was for second line. With that, we realized that this compound had activity and was safe. But it was restricted for [patients with] ring sideroblastic anemia. Here what we did was to move this to frontline so patients [on trial] had not been treated with an ESA; these were patients [who] were transfusion dependent. We did a 1:1 randomization between luspatercept and a commonly-used ESA. This was for all comers [with] low-risk MDS, so it was not restricted to SF3B1 mutations or [ring sideroblast]-positive disease. What is important is that they had a very strong primary end point where not only [did] we measure the degree of transfusion independence, but also the increase in hemoglobin levels.

1:01 | On this randomized, [non-]blinded study, we showed that not only their response with luspatercept was significantly superior to that of a standard ESA, but in my opinion, the duration of response actually was significantly longer. The quality of responses were significant and important...passing over a year very significantly. So it's not only their responses, it's the duration of response. Then in general, [there was] an excellent toxicity profile with this compound that makes it now probably a strong choice for first-line therapy in anemic patients with MDS.

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