Implications of the Full Analysis of the COMMANDS Trial of Luspatercept for MDS

A roundtable discussion, moderated by Hana Safah, MD, of the Tulane University School of Medicine, focused on the latest data in myelodysplastic syndromes presented at the 65th ASH Annual Meeting & Exposition. Dr. Safah was joined by Jamile Shammo, MD; Andrew Brunner, MD; and Tiffany Tanaka, MD.

In the next segment of the roundtable series, Dr. Safah outlines the findings from the full analysis of the COMMANDS trial presented at the ASH 2023 Annual Meeting.

Watch the next segment in this series.

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Dr. Safah: Because of the MEDALIST trial, luspatercept was approved in 2020 for patients who have either failed or couldn’t receive or were not expected to respond to epoetin. From there comes the COMMANDS trial. The COMMANDS trial interim analysis was presented in ASCO last year and it showed again, the eligibility criteria was a little bit different from the MEDALIST trial. The patients there were patients who were treatment-naïve, so they have not seen the erythropoietin treatment before and they could have RS [ring sideroblast]-positive, RS-negative, although 75% of them were RS-positive for reasons that we think we know why.

But also they had to have erythropoietin of less than 500, and patients should have had a blast count of less than 5%. When we look at the efficacy data, and the primary endpoint was looking at transfusion independence for 12 weeks as well as combined with increase in the hemoglobin of 1.5 g/dL within week one through week 24. The data was significantly better in the luspatercept arm compared to the erythropoietin arm, 60% compared to around 30%. It was well tolerated and had a good outcome in all the subgroups. They showed that patients did better with luspatercept, whether they are the mutated type SF3B1, the unmutated type, RS-positive, erythropoietin levels of less than 200, 200 to 500. However, it was compatible between in the RS-negative group to erythropoietin. We’ll have some discussions later to understand probably we have some explanations for that.

Now, what we’re going to see in ASH is the updated analysis or the full analysis of the COMMANDS trial with more time. Duration of treatment in the luspatercept was around 51 weeks and the erythropoietin arm was around 37 weeks. Then we see with the extension of the period of time of treatment, the same results continued to be seen with almost 60% transfusion independence for 12 weeks with week one to week 24 in the luspatercept arm compared to around 34% in the erythropoietin arm. Again, there were significantly better results with the luspatercept compared to the erythropoietin. What also held is exactly the same sub-analysis that we saw earlier, that the improvement was seen in the SF3B1-positive patients as well as the wild RS-positive, with the erythropoietin level being less than 200 and 200 to 500, however compatible, the results continue to be seen in the RS-negative between the luspatercept and the erythropoietin.

But again, when we look at safety, there was no increase in the safety signals. It was well tolerated, similar to what we saw in the interim analysis—hypertension, asthenia—there was nothing that evolved with longer treatment and longer follow-up. That’s what we’re going to see. To me, as a physician who takes care of patients with MDS [myelodysplastic syndromes], again, the majority of those patients are with low-risk MDS and the anemia and some of them are transfusion dependent. The question here comes we’re seeing improvement, so we’re going to give a treatment that is every three weeks compared to weekly, that’s going to result with less transfusion dependent and more patients becoming transfusion independent. Less complications from transfusions. I’m hoping we’re going to discuss quality of life in one of the abstracts.

But again, my colleagues always ask me, should it be only for patients who are transfusion-dependent? The FDA gave it the approval recently for patients who are transfusion-dependent as well as might be or could be. I think that’s an important point, and we should not take it lightly. Maybe we should talk about when should we start such treatment? Should we wait until they become transfusion-dependent? Again, there are abstracts that is showing maybe it is better to start it early on to prevent the transfusion dependency and the complications that come with that.