Expert discusses analysis of phase 3 MEDALIST trial data aimed to assess the probability of greater overall survival and progression-free survival benefit from luspatercept vs placebo.
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 “Overall Survival [OS] and Progression-Free Survival [PFS] of Patients Following Luspatercept [Reblozyl; Celgene Corporation] Treatment in the MEDALIST Trial” at the 64th American Society of Hematology (ASH) Annual Meeting and Exhibition in New Orleans, Louisiana.
Pharmacy Times®: Why is overall survival in patients with lower-risk myelodysplastic syndromes important to assess?
Uwe Platzbecker: In general, I think, in every malignancy, overall survival is the main driver—or improvement of overall survival is the main driver of clinical trials, and also the administration of novel agents, I think, is aimed to improve survival of patients.
Low risk MDS patients, especially those with ring sideroblasts phenotype, have a rather good or decent survival compared to other subtypes of MDS, so I think to basically show a survival benefit with a given drug is not easy to achieve. Therefore, I think it is very important to do also analysis with regards to the survival benefit in clinical trials in [patients with low risk MDS].
The MEDALIST trial was actually not powered to show this survival difference with the 2 arms, but I think it's the analysis shown in the poster presentation, I think is very valid and also important for clinical decision making.
Pharmacy Times®: What did the phase 3 MEDALIST trial results show regarding overall survival benefit of luspatercept in patients with lower-risk myelodysplastic syndromes?
Uwe Platzbecker: The data actually showed that achieving a response with luspatercept treatment increased the overall survival probability, which I think is, of course, something which we observe also with other drugs, that achieving a response, I think is a selection of a patient population with maybe rather good or good risk disease characteristics, but I think it is important also, when you have a patient and you treat the patient and the patient is responding, I think this brings the patient into a situation where maybe the survival estimate is improved just by the treatment with a given agent.
Pharmacy Times®: What did the trial results show regarding progression-free survival?
Uwe Platzbecker: Luspatercept was not only associated with an increased 3-year, overall survival probability for patients with IPSS-R very low risk MDS, but also a 3-year progression free survival in patients with a baseline serum equal level of 100 to less than 200. So this is, I think, interesting and patients with low risk MDS with these baseline characteristics may therefore derive a greater survival benefit, also progression free survival benefit, from luspatercept, and I think the future studies, which are currently already ongoing with a longer follow up times, may also help to clarify the long term impact of luspatercept therapy.
Pharmacy Times®: What are the implications of these phase 3 results?
Uwe Platzbecker: I think it will be very important to study patients on long term benefit: who are those patients [and] what are also the molecular disease characteristics? So I think it could be very important to stratify—for instance, patients at the very beginning of their therapy—stratify in a way maybe that single agent luspatercept may be valid for as for a specific subset of patients who can stay on therapy for a long time, but may not be enough for another still-to-be-defined subset of patients where add-on strategies with novel agents, for instance, also agents not-so-novel like [epoetin (Epogen; Amgen)] or lenalidomide (Revlimid; Celgene Corporation) may help to basically induce responses, especially long-term responses, and by doing so, have a potential disease modifying activity.