Expert: Phase 3 MEDALIST Trial Results Show ‘Red Blood Cell Transfusion Independence for Substantial Period of Time’ in LR-MDS


Expert discusses the effect of baseline transfusion burden and luspatercept dose level on response to treatment in patients with LR-MDS from the MEDALIST study.

Pharmacy Times® interviewed Uwe Platzbecker, MD, director of the Clinic and Polyclinic, Hematology, Cell Therapy, and Hemostaseology, Leipzig University Hospital, on the poster presentation titled “Multiple Episodes of Transfusion Independence with Luspatercept [Reblozyl; Celgene Corporation] Treatment and the Impact of Dose Escalation in Patients with Lower-Risk Myelodysplastic Syndromes [LR-MDS] from the MEDALIST Study” at the 64th American Society of Hematology (ASH) Annual Meeting and Exhibition in New Orleans, Louisiana.

Pharmacy Times®: What did the phase 3 MEDALIST trial look to assess?

Uwe Platzbecker: So the primary goal of the MEDALIST trial was to assess and also compare the efficacy of luspatercept compared to placebo in patients being red blood cell transfusion dependent, with so called [lower risk] MDS and also being refractory before or not eligible for a standard of care treatment with erythropoiesis stimulating agents.

Pharmacy Times®: What was the primary endpoint of the trial, and what did the results show for patients who achieved this endpoint?

Uwe Platzbecker: So the primary endpoint of the trial was red blood cell transfusion independence for more than 8 weeks within the first 24 weeks of treatment and the comparison [of] luspatercept versus placebo showed a significant difference with regards to the primary endpoint with roughly 50% of the patients achieving a response to luspatercept and 15% of the patients receiving a response to the placebo. So the trial was actually positive and also led to the registration of luspatercept in the given indication.

Pharmacy Times®: What did the trial results show regarding patient response periods to treatment?

Uwe Platzbecker: The findings, actually, with regards to the response periods to treatment, were quite novel because there was a substantial amount of patients who basically responded [by] becoming red blood cell transfusion independent for a substantial period of time, and then get another transfusion event but then achieved a second, third, or sometimes even more than this period of red blood cell transfusion independence. So I think this is an important result of the trial that patients who achieved a response and then lose the response by, again, receiving a transfusion can achieve multiple periods of response to treatment.

Pharmacy Times®: What did the results show regarding dose escalation in patients with lower-risk myelodysplastic syndromes?

Uwe Platzbecker: The trial actually mandated dose escalation in patients not responding up to the maximum dose of luspatercept being 1.75 milligram per kilogram given every 3 weeks as a subcutaneous injection. So this was mandated during the trial, and what I think is a major result of the study is that—especially patients with so called intermediate or high transfusion burden, so patients getting more than 4 units of red blood cells within 8 weeks prior to the study entry—the majority of them required actually a dose escalation in order to achieve a response but also to maintain the response.

Pharmacy Times®: What are the implications of these results and potential next steps?

Uwe Platzbecker: I think first implication from a clinical perspective is that patients achieving a response and then getting another transfusion event should be kept on [the] drug, and in order to assess whether another subsequent response period can be achieved. And secondly, I think that dose escalation is very important in order to achieve the optimal response, especially in patients with high transfusion burden.

Next steps could be and are already clinical studies where maybe the starting dose of luspatercept could be the maximum available starting dose according to the prescribing information. So starting with a maximum dose may yield higher response rates and maybe also more durable response rates, and this is actually studied in a prospective clinical trial already.

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