ASH 2023 | Trial updates for luspatercept in LR-MDS: COMMANDS, MEDALIST and ELEMENTS-MDS
Amer Zeidan, MBBS, Yale Cancer Center, New Haven, CT, gives an overview of the clinical trials that have evaluated the efficacy and safety of luspatercept in patients with low-risk myelodysplastic syndromes (LR-MDS). These include the MEDALIST trial (NCT02631070), which evaluated luspatercept versus placebo in patients intolerant/refractory to erythropoesis-stimulating agents (ESAs), with transfusion independence occurring in almost 40% vs 15% of patients, respectively. Additionally, the COMMANDS (NCT03682536) study evaluated luspatercept in the front-line setting versus ESAs. Updates from both of these studies were reported at the ASH 2023 meeting. Dr Zeidan also tells us about the ongoing ELEMENT-MDS (NCT05949684) study, which is evaluating the efficacy and safety of luspatercept vs epoetin alfa for the treatment of anemia in adults with LR-MDS who are not yet transfusion-dependent. This interview took place at the 65th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript (edited for clarity)
Yeah, so luspatercept is a protein, it’s a fusion protein that targets the ligands of the transforming growth factor beta pathway. Those ligands have been shown in patients with lower-risk MDS to drive ineffective erythropoiesis, leading to anemia in patients with lower-risk MDS. And indeed, the use of luspatercept has been shown in Phase II data, in the PACE trial, to improve the rate of transfusion independence, and subsequently in the MEDALIST trial, which was a randomized study of luspatercept against placebo after ESA failure, to lead to transfusion independence in almost 40%, compared to 15% of patients...
Yeah, so luspatercept is a protein, it’s a fusion protein that targets the ligands of the transforming growth factor beta pathway. Those ligands have been shown in patients with lower-risk MDS to drive ineffective erythropoiesis, leading to anemia in patients with lower-risk MDS. And indeed, the use of luspatercept has been shown in Phase II data, in the PACE trial, to improve the rate of transfusion independence, and subsequently in the MEDALIST trial, which was a randomized study of luspatercept against placebo after ESA failure, to lead to transfusion independence in almost 40%, compared to 15% of patients. After that, luspatercept was moved to the frontline setting in the COMMANDS trial, which tested patients who received luspatercept against ESA as a frontline treatment in patients with lower-risk MDS who are transfusion-dependent and who had anemia. And this trial was positive. It was reported last year, or sorry earlier this year, and the paper was just published in The Lancet.
In this ASH, we report updates from the COMMANDS trial, which shows the final analysis, as well as an update from the MEDALIST trial, the first trial that led to the approval of luspatercept, where we confirmed the risk of the transfusion independence and that patients achieved durable transfusion independence with the drug.
I also like to point out that we have a trial that just started, another large Phase III trial with the drug, called ELEMENT, which we look at patients who are not yet transfusion-dependent. So those are patients who have symptomatic anemia similar to the COMMANDS trial, but they are not yet needing transfusions. And the similar randomization to luspatercept versus EPO. And I think this could be a major change in the landscape of management of lower-risk MDS, because historically we have not treated patients with lower-risk MDS who are not yet transfusion-dependent. So if that trial is positive, I think it could be a major change in the way we think about management of those patients.
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Disclosures
Consultancy: Schrödinger, Notable, Chiesi, Mendus, Otsuka, Foran, Syros, ALX Oncology, Kura, Seattle Genetics, Servier, Boehringer-Ingelheim, Jazz, Orum, Geron, Syndax, Gilead, Zentalis, BeyondSpring, Incyte, Pfizer, Celgene/BMS, Janssen, Amgen, Agios, Daiichi Sankyo, Tyme, Taiho, AbbVie, Ionis, Takeda, Genentech, Epizyme, Lox Oncology, Novartis, Astellas, BioCryst, Regeneron
Honoraria: Schrödinger, Notable, Chiesi, Mendus, Otsuka, Foran, Syros, ALX Oncology, Kura, Seattle Genetics, Servier, Boehringer-Ingelheim, Jazz, Orum, Geron, Syndax, Gilead, Zentalis, BeyondSpring, Incyte, Pfizer, Celgene/BMS, Janssen, Amgen, Agios, Daiichi Sankyo, Tyme, Taiho, AbbVie, Ionis, Takeda, Genentech, Epizyme, Lox Oncology, Novartis, Astellas, BioCryst, Regeneron
Research Funding: Foran, Shattuck Labs, Astex
