Luspatercept appears to improve the rate of blood transfusion independence among a subset of patients with myelodysplastic syndromes (MDSs), according to research published in The Lancet.

There was no previous study into whether luspatercept is superior to erythropoiesis-stimulating agent (ESAs) for the treatment of ESA-naïve patients with lower-risk MDS who are transfusion-dependent.

For the ongoing phase 3 COMMANDS study ( Identifier: NCT03682536), researchers are comparing the safety and efficacy of luspatercept with epoetin alfa in this patient population. In the present paper, researchers reported an interim analysis from COMMANDS.

Continue Reading

Overall, 356 patients were enrolled and randomly assigned to receive luspatercept (178 patients) or epoetin alfa (178 patients). In the total cohort, the median age was 74 years at baseline, 56% of patients were men, 68% of patients had a MDS with multiple lineage dysplasia and ring sideroblasts, 61% of patients had mutant SF3B1, and 37% of patients required at least 4 units for red blood cell transfusions per 8-week period.

The interim efficacy analysis included 301 patients (147 and 154 patients in the luspatercept and epoetin alfa groups, respectively). All patients included had either completed 24 weeks of treatment or had discontinued treatment prior to this point.

In the luspatercept and epoetin alfa groups, 59% and 31% of patients, respectively, reached the primary endpoint of red blood cell transfusion independence for at least 12 weeks, including a mean consistent hemoglobin increase of at least 1.5 g/dL. This finding corresponded to a common risk difference on response rate of 26.6 (P <.0001).

Furthermore, the median treatment exposure was longer in the luspatercept group (42 weeks) than in the epoetin alfa group (27 weeks).

Serious treatment-related adverse events noted in the luspatercept group included fatigue, asthenia, nausea, dyspnea, hypertension, and headache — all of which occurred in at least 3% of patients. None of these events were noted in at least 3% of patients in the epoetin alfa group. One patient died after an acute myeloid leukemia diagnosis, which was considered related to luspatercept.

“The findings from this planned interim analysis suggest that luspatercept could provide an alternative to the current standard-of-care treatment for anaemia in patients with lower-risk myelodysplastic syndromes with or without ring sideroblasts who require red blood cell transfusions,” the authors wrote in their report.

Disclosures: This research was supported by Celgene and Acceleron Pharma. Please see the original reference for a full list of disclosures.


Platzbecker U, Della Porta MG, Santini V, et al. Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): Interim analysis of a phase 3, open-label, randomised controlled trial. Lancet. Published online June 9, 2023. doi:10.1016/S0140-6736(23)00874-7