Dr Platzbecker on the COMMANDS Trial in Lower-Risk MDS With Anemia

Uwe Platzbecker, MD, director, Medical I, University Hospital Leipzig, discusses key findings from the phase 3 COMMANDS trial (NCT03682536) with luspatercept-aamt (Reblozyl) in patients with lower-risk myelodysplastic syndrome (MDS) with anemia, as well as the clinical implications of FDA approval of luspatercept for patients in this population.

On August 28, 2023, the FDA approved luspatercept for the treatment of anemia in erythropoietin stimulating agent (ESA)–naïve patients with very low– to intermediate-risk MDS who may require regular red blood cell (RBC) transfusions. This regulatory decision was backed by interim findings from the phase 3 COMMANDS trial, which evaluated luspatercept vs the ESA epoetin alfa in patients with MDS with who had not received prior ESAs and required RBC transfusions. Patients were enrolled regardless of ring sideroblast status. In COMMANDS, 58.5% of patients who received luspatercept achieved RBC transfusion independence of at least 12 weeks with a concurrent mean hemoglobin increase of at least 1.5 g/dL in weeks 1 to 24 vs 31.2% of those who received epoetin alfa.

The FDA approval of luspatercept provides oncologists practicing in the United States with the choice of administering this agent in the frontline setting for ESA-naïve patients with lower-risk MDS with anemia, irrespective of ring sideroblast status, Platzbecker says. In COMMANDS, patients with ring sideroblast–positive disease achieved favorable response rates with luspatercept compared with epoetin alfa, Platzbecker explains. The response rates with luspatercept in the ring sideroblast–negative population were similar to those with epoetin alfa, according to Platzbecker. However, the patients who received luspatercept experienced a longer duration of response than those who received epoetin alfa, Platzbecker notes. These data support the use of luspatercept as the preferred frontline treatment for patients with ring sideroblast–positive disease, Platzbecker emphasizes.

The choice of treatment for patients with ring sideroblast–negative disease should be determined by each patient’s treating hematologist/oncologist, Platzbecker says. Many factors can influence this decision, including patient preferences regarding the dosing schedule and administration method of each drug, Platzbecker notes. For instance, in COMMANDS, patients received either subcutaneous luspatercept starting at 1.0 mg/kg once every 3 weeks or epoetin alfa starting at 450 IU/kg once weekly.

Additional data are needed to understand which patients with ring sideroblast–negative disease may benefit most from treatment with luspatercept, Platzbecker emphasizes. However, the FDA approval of luspatercept in patients with lower-risk MDS with anemia is paradigm shifting, and the approval of this agent in the European Union is anticipated, Platzbecker concludes.