COMMANDS trial heralds ‘paradigm shift’ for anemia associated with lower-risk MDS

medwireNews: Luspatercept almost doubles the likelihood of achieving transfusion independence with hemoglobin increase relative to epoetin alfa in erythropoiesis-stimulating agent (ESA)-naïve patients with anemia due to lower-risk myelodysplastic syndromes (LR-MDS), shows a phase 3 trial. The results of the preplanned interim analysis were presented at the EHA2023 Hybrid Congress in Frankfurt, Germany, by Matteo Giovanni Della Porta (Cancer Center IRCCS Humanitas Research Hospital, Milan, Italy). He told the audience that “[l]uspatercept is the first and only therapy to demonstrate superiority in a head-to-head study against ESAs and brings a paradigm shift in the treatment of LR-MDS–associated anemia.” The COMMANDS trial participants – who had very low-, low-, or intermediate-risk disease as per the Revised International Prognostic Scoring System and had required red blood cell (RBC) transfusions for at least 8 weeks – were randomly assigned to receive at least 24 weeks of treatment with subcutaneous luspatercept at a dose of 1.0–1.75 mg/kg every 3 weeks (n=178) or epoetin alfa at a weekly dose of 450–1050 IU/kg (n=178). In the current analysis, which included 301 patients who completed 24 weeks of treatment or discontinued earlier, the primary endpoint of RBC transfusion independence for at least 12 weeks with a concurrent mean increase in hemoglobin levels of at least 1.5 g/dL was achieved by 58.5% of luspatercept-treated patients and 31.2% of those give epoetin alfa, a significant difference. “Achievement of the primary endpoint favored luspatercept or was similar to epoetin alfa for all subgroups analyzed,” highlighted the presenter. For instance, in patients with ring sideroblast-positive status, the rate of transfusion independence with hemoglobin increase was 64.8% with luspatercept and 25.9% with epoetin alfa. The corresponding rates in ring sideroblast-negative patients were 41.0% and 46.3%. Luspatercept was also superior to epoetin alfa with regard to key secondary outcomes. For example, the proportion of patients who had a hematologic improvement–erythroid response that lasted at least 8 weeks was significantly higher in the luspatercept than epoetin alfa group, at 74.1% versus 51.3%. And in the subset of participants who were RBC transfusion independent for 12 weeks or more, the median duration of transfusion independence was significantly longer with luspatercept, at 126.6 weeks versus 77.0 weeks with epoetin alfa. Della Porta said that “luspatercept was associated with a very good safety profile that was consistent with previous clinical experience.” The rates of treatment-emergent adverse events were “balanced between arms,” even though the median duration of treatment was nearly doubled with luspatercept compared with epoetin alfa (41.6 vs 27.0 weeks), he continued. The COMMANDS data were concomitantly published in The Lancet and previously presented at the 2023 ASCO Annual Meeting in Chicago, Illinois, USA. medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group EHA2023 Hybrid Congress; Frankfurt, Germany & Virtual: 8–15 June Lancet 2023; doi:10.1016/S0140-6736(23)00874-7 2023 ASCO Annual Meeting; Chicago, Illinois, USA: 2–6 June

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COMMANDS trial heralds ‘paradigm shift’ for anemia associated with lower-risk MDS

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