Dr Sallman on the Significance of the FDA Approval of Luspatercept for Lower-Risk MDS

David Sallman, MD, assistant member, Department of Malignant Hematology, Moffitt Cancer Center, discusses the clinical implications of the 2023 FDA approval of luspatercept-aamt (Reblozyl) for the treatment of anemia in patients with very low– to intermediate-risk myelodysplastic syndrome (MDS). Notably, the agent was approved forthose without prior erythropoiesis-stimulating agent (ESA) use who may require regular red blood cell (RBC) transfusions.

The regulatory approval of luspatercept was supported by interim findings from the phase 3 COMMANDS trial (NCT03682536). Treatment with luspatercept demonstrated superior rates of concurrent RBC transfusion independence (RBC-TI) and hemoglobin (Hb) increase vs treatment with epoetin alfa, irrespective of ring sideroblast status. As such, 58.5% (n = 86) of patients who were treated with luspatercept achieved the primary end point of RBC-TI of at least 12 weeks with a mean Hb increase of at least 1.5 g/dL within the first 24 weeks vs 31.2% (n = 48) of those given epoetin alfa (P < .0001).

Sallman says that in patients with MDS with ring sideroblasts, luspatercept is the most effective frontline therapy. In COMMANDS, the overall response rate with luspatercept was high, particularly in patients who were transfusion-dependent, he explains. For optimal treatment decisions, it is essential to perform a bone marrow biopsy and conduct molecular testing for the SF3B1 mutation, Sallman notes. This ensures accurate diagnosis, as ring sideroblasts may be missed during staining, according to Sallman. Despite luspatercept’s proven efficacy in this population, its widespread adoption has not yet occurred in the broader medical community, though this agent should be more universally accepted as the optimal therapy for MDS with SF3B1 mutations, he expands.

However, the use of luspatercept in non–ring sideroblast cases is controversial, Sallman continues. Althoughoutcomes with luspatercept vs epoetin alfa were not inferior in these patients, the agent’s superiority was not dramatic, he states. Erythropoietin levels are also a key consideration, as patients with levels greater than 200 U/L tend to respond less well to ESAs than those with lower levels, he emphasizes. This strengthens the case for the use of luspatercept in this group, he notes. Although opinions may differ on whether luspatercept should be applied universally in MDS, it has undeniably revolutionized the treatment of frontline patients with MDS harboring SF3B1mutations, with most of these patients achieving a favorable response with the agent, Sallman concludes.