REBLOZYL, also known as luspatercept, is a medication that promotes the development of mature and functional red blood cells by supporting the growth of erythroid cells in the bone marrow. It achieves this by interacting with specific substances in the TGF-β superfamily, preventing abnormal signaling through the Smad2/3 pathway. REBLOZYL is already approved for use in patients with transfusion-dependent, lower-risk Myelodysplastic Syndrome with ringed sideroblasts or myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis, but only after failure of an ESA. The COMMANDS trial specifically focused on the first-line use of luspatercept in patients with transfusion-dependent, lower-risk Myelodysplastic Syndrome with or without ringed sideroblasts and with <5% bone marrow blasts.
In the Phase III study (NCT03682536) involving 301 patients who had not received any previous erythropoiesis-stimulating agents (ESAs), the effectiveness of luspatercept and epoetin alfa was assessed through an interim analysis. The results showed that 58.5% of the patients treated with luspatercept achieved the primary endpoint, compared to only 31.2% of those treated with epoetin alfa. Additionally, various other indicators of improved blood cell production and reduced dependence on transfusions were significantly more favorable for patients receiving luspatercept compared to those receiving epoetin alfa.
During the initial 24 weeks of the study, the interim findings revealed that luspatercept led to higher hemoglobin levels and enabled almost twice as many patients to avoid the need for red blood cell transfusion compared to epoetin alfa. Furthermore, the interim analysis revealed that the median duration until the first red blood cell (RBC) transfusion was 168 days for patients who received luspatercept, whereas it was 42 days for patients who received epoetin alfa. Among the subgroup of patients who achieved a minimum of 12 weeks of independence from RBC transfusions, the median duration of response was significantly longer with luspatercept compared to epoetin alfa. Specifically, it was 2.43 years for luspatercept and 1.48 years for epoetin alfa, indicating that the beneficial effects of luspatercept lasted for approximately one year longer than those of epoetin alfa.
In addition to achieving the main objective of the study in the overall patient population, luspatercept demonstrated an improved response compared to epoetin alfa across nearly all subgroups of patients, particularly those with ringed sideroblasts or SF3B1 mutations. While there was a slightly higher occurrence of treatment-emergent adverse events (AEs) among patients receiving luspatercept compared to epoetin alfa (92.1% vs. 85.2%), it is worth noting that patients treated with luspatercept remained on the therapy for a longer duration compared to those treated with epoetin alfa.
KOL insights
“The COMMANDS results could transform how we approach the treatment of anemia in patients with lower-risk Myelodysplastic Syndrome. They suggest that luspatercept could represent the standard of care as first-line therapy for a significant fraction of patients with anemia and lower-risk disease.” – Expert Opinion.
“I believe that the findings of this trial establish luspatercept as the standard of care for ESA-naive, lower-risk Myelodysplastic Syndrome patients [who] do not have del(5q) with transfusion-dependent anemia” – Expert Opinion.
Conclusion
The findings from the Phase III COMMANDS trial provide strong support for the utilization of luspatercept in patients with transfusion-dependent, lower-risk myelodysplastic syndromes (MDS). The trial demonstrated that luspatercept is a well-tolerated and more effective alternative to epoetin alfa as a first-line treatment for managing anemia in these patients. The trial successfully achieved its primary goal, which was to attain a minimum duration of 12 weeks without requiring red blood cell (RBC) transfusions, along with a mean increase in hemoglobin levels of at least 1.5 g/dL within the initial 24 weeks of the study. Additionally, all secondary endpoints were also met by the trial.
Get a more detailed overview of the key developments in the domain at: Myelodysplastic Syndrome Market, Myelodysplastic Syndrome Epidemiology Forecast, Myelodysplastic Syndrome Pipeline Insight
