1-Year Follow-up of Efficacy Data and Safety Outcomes of Imetelstat in Lower-Risk MDS

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

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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

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: I mentioned a little bit on the 28 week, Amer, whatever happened in the longer follow-up? Can you talk a little bit about that?

Dr. Amer Zeidan: Yeah. I think the points that you raise are very important because it's not common to have a drug from the data that we have seen so far in many of the evolving drug to have such a durable response. So the bottom line number, the main number is a 40% transfusion independence, the eight week. But once you look at that, the 24 week transition independence it's normal that it gets a little bit lower. It's 28% at 24 weeks. The one year, based on the update that Dr. Platzbecker presented in year 2023, the cutoff of the data on that update was up to January, 2023. It was 18% transfusion independence rate. This is from everybody who was responding initially. So it's durable. The median duration as you mentioned is pretty good. But I think I also like to emphasize the degree of the hemoglobin rise was quite amazing to me. So those patients started with around hemoglobin level of eight on both arms. Among the responders, the hemoglobin did not go up by one. It went up by three and a half grams. It went all the way from eight grams to three and a half grams. This kind of increases we have not seen with any drug short of lenalidomide with Del(5q) where the median rise was around four and a half gram. So this I think, a very solid signal when you take that with the durability, when you take that with the high response rate and the fact that the patient's transfusion burden, as I mentioned, was six units on average. That's a lot of transfusions. And to have among those patients who have high transfusion burden, one third of them became transfusion independent. Going all the way from six units, one unit every week to complete transfusion independence is very, very good. Especially that we also saw the same signal in RS negative patients, which as you mentioned with Luspatercept, it doesn't seem to work very well. It does work, but not as good in that second line setting compared to what we're seeing with imetelstat. It's I think a very interesting drug. I think the data regarding potential disease modification is something we'll probably discuss in a little bit as well. But this is also one of the aspects that particularly excites me in particular about the drug. But before we go to that, maybe you can, Mike, discuss some of the safety data. Because you mentioned there was a concern about a liver signal early on with the higher doses really. With the 9.6 milligram per kilogram dose that was used in myelofibrosis. But this did not seem to replicate in the MDS studies that use the 7.5 lower gram in the IMerge study.

Dr. Michael Savona: That's completely right. There really wasn't a signal with this larger phase three population. The two to one randomization kind of makes us feel even more comfortable. 118 patients treated with this dose of imetelstat and really no difference. So I think for the non-hem folks, there's really not too much to worry about. The main thing really is the hem tox, which there is some neutropenia and some thrombocytopenia. But the important thing is there's no increase in bleeding events. The neutropenic fever rates were not particularly high. Both of these cytopenias reverse over time, which are all kind of for people like us who take care of MDS, this is really not a big deal. I think from a safety perspective, you've got very manageable cytopenias. These are fleeting cytopenias. The consequences of cytopenias did not really lead to much of a difficulty. I do want to comment on something you said that just to underscore.