COMMANDS trial: A paradigm shift in LR-MDS-associated anaemia

Luspatercept was superior to epoetin alfa in treating anaemia in erythropoiesis-stimulating agent (ESA)-naïve patients with transfusion-dependent lower-risk myelodysplastic syndromes (LR-MDS). The safety profile of luspatercept was manageable and predictable.

Luspatercept has been shown to improve erythropoiesis and increase platelet and neutrophil counts in patients with LR-MDS [1,2]. Dr Matteo Della Porta (Humanitas Cancer Centre Milan, Italy) presented the results of an interim analysis of the phase 3 COMMANDS trial (NCT03682536), which compared luspatercept with ESAs in ESA-naïve participants with transfusion-dependent LR-MDS [3]. The study randomised 356 participants 1:1 to luspatercept or epoetin alfa for the treatment of anaemia. The primary endpoint was red blood cell transfusion independence for at least 12 weeks during the 24-week treatment period with a concurrent mean haemoglobin increase of at least 1.5 g/dL.

Luspatercept outperformed epoetin alfa for the primary endpoint: 58.5% of the participants in the experimental arm achieved the primary endpoint versus 31.2% in the control arm (P<0.0001). All subgroup analyses favoured treatment with luspatercept over epoetin alfa, except for the subgroup of participants without ring sideroblasts. Dr Della Porta highlighted the results of an exploratory analysis where participants with SF3B1, SF3B1a, ASXL1, and TET2 mutations were likely to benefit significantly more from luspatercept than from epoetin alfa.

The treatment discontinuation rate was 44% in the luspatercept and 60% in the epoetin alfa arm. Lack of efficacy was the main reason for treatment discontinuation in the luspatercept (15.7%) and epoetin alfa arm (32.4%). Finally, treatment-emergent adverse events were balanced between the two arms, including low rates of progression to acute myeloid leukaemia.

1. Fenaux P, et al. N Eng J Med. 2020;382:140–151
2. Garcia-Manero G, et al. 2022;139(4):624–629
3. Della Porta MG, et al. Luspatercept versus epoetin alfa for treatment of anemia in ESA-naïve lower-risk myelodysplastic syndromes patients requiring RBC transfusions: data from the phase 3 COMMANDS study. Plenary abstracts session, EHA 2023 Annual Congress, 8─11 June, Frankfurt, Germany.

Copyright ©2023 Medicom Medical Publishers



Posted on 2 August 202327 March 2024