ASH 2024 | HRQoL outcomes with luspatercept vs epoetin alfa in transfusion-dependent LR-MDS: COMMANDS analysis

The COMMANDS study is a randomized global trial comparing luspatercept and epoetin alfa for low-risk myelodysplastic syndromes with anemia requiring transfusions. So the results of the trial for the primary efficacy endpoint have been already published, where luspatercept is superior to epoetin alfa in inducing transfusion independence for the duration of at least 12 weeks and a concomitant rise in 1.5 grams per deciliter hemoglobin. We have previously reported also the benefits in terms of patient reported outcomes of reaching this endpoint showing more benefit in the luspatercept versus the epoetin alfa in improving patient-reported outcomes. However, when we pooled the patients to analyze the significance of increasing hemoglobin levels, we found a threshold of 10 grams per deciliter of hemoglobin to induce a patient perceived response, so a benefit in terms of fatigue and dyspnea with respect to those who reached the endpoint but did not go beyond 10 grams per deciliter. 

So at this point, in the poster that I’m presenting this afternoon, we are reporting the sustained benefit in patient reported outcomes which was prevalent in the luspatercept arm compared to the epoetin alfa where 30% of patients reached a sustained benefit with luspatercept versus about 20% in the epoetin, and this was for the FACT anemia, the FACT fatigue scores and the EORTC QLQ fatigue scores. Furthermore we wanted to see whether reaching a sustained benefit was earlier for luspatercept versus epoetin alfa and this was true for almost all of the FACT anemia subscales. Now we also wanted to see, for those patients who had a good quality of life at the time of enrollment, whether the time to deterioration was in favor of one or the other drug and it was in favor of luspatercept, deterioration meaning at relapse at the time of a transfusion. So luspatercept delayed relapse with transfusion so the duration is longer with luspatercept and this is also associated with a delay in worsening of patient reported outcomes, and this was true for all the domains of the FACT and of the EORTC QLQ-C30. This shows that luspatercept is an appropriate drug for first-line treatment of patients with low-risk myelodysplastic syndromes requiring transfusions.

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