Insights on Imetelstat in Lower-Risk MDS: Safety Outcomes

EP: 1.Understanding Myelodysplastic Syndrome: Molecular Mechanisms and Diagnosis

EP: 2.Defining and Assessing Risk in Patients with Myelodysplastic Syndrome

EP: 3.First-Line and Second-Line Treatment Options for Lower-Risk MDS

EP: 4.Imetelstat in Lower-Risk MDS: IMerge Trial Overview and Efficacy Outcomes

EP: 5.1-Year Follow-up of Efficacy Data and Safety Outcomes of Imetelstat in Lower-Risk MDS

EP: 6.Disease Modifiying Therapy in Lower-Risk MDS

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EP: 7.Insights on Imetelstat in Lower-Risk MDS: Safety Outcomes

EP: 8.Clinical Implications and Positioning of Imetelstat in Lower-Risk MDS

Dr. Michael Savona: We talked about the clone. We talked about the key efficacy measures. I mentioned briefly patients fatigued. There we used the Facit fatigue scoring system in this trial. This is a validated instrument to test patient reported fatigue specific. Because the MDS fatigue is number one in the symptoms. It's the big one. What's important to note is that basically the scoring was not that different in patients with placebo or imetelstat except for the fact that the patients who had resolution of fatigue, it happened in about a half a year in imetelstat group, and it took like a year in the placebo group. So clearly, if people are getting relief of fatigue, it happens faster. But importantly, unlike a lot of the other drugs I mentioned before, Luspatercept with profound fatigue in that first cycle, there doesn't really seem to be an increase in fatigue with this drug. I think we deal with a lot of drugs that cause a lot of side effects in patients, and we have strong stomachs to be able to get patients through these things. But it's nice to be able to put someone on a drug that they actually tolerate and don't have a lot of toxicity. We get a little bit of nausea with this agent, that's fairly manageable. But the fatigue not getting worse and the manageable reversible cytopenias, I think are really good news. So we're kind of coming up to the end of the hour and I want to talk philosophically a little bit more with you, Amer. We don't get this opportunity very often and you have a lot of deep insight into how this kind of drug works. So what do you think, first on the clinical side. All this data being explained, where do you think imetelstat fills a need? Where does it kind of go into the sequencing of treatment of patients with MDS?

Dr. Amer Zeidan: That's a very good question. I mean, I think in my opinion, the data is quite solid and I think it's extremely likely that the drug will be approved for the indication which is in the second line setting after ESA failure. We kind of emphasize this point I think multiple times, but the degree of transfusion independence and among heavily transfusion dependent patients has been actually a big problem for us because most of the drugs that we have don't work very well when the patient is needing a lot of transfusion including Luspatercept. So Luspatercept is a very good drug in the second line setting for patients who are ringed sideroblasts plus positive, and patients who do not need a lot of transfusion. Actually in the sub-analysis of the Medalist trial, once you need more than six units of blood per eight weeks, the transfusion dependence rate goes to 9%. Very low, like 1 out of 10. Here, I think with imetelstat the transfusion dependence rate for patients who need more than six units is 33%. One third of those patients will become completely transfusion independent. I think the durability as well the degree of the hemoglobin rise between all of this, I think in the second line setting I think for patients who are ringed sideroblasts plus negative, and for patients who are heavily transfusion dependent, I think imetelstat is going to change the way we practice. It's certainly a practice changing trial.