A roundtable discussion, moderated by Guillermo Garcia-Manero, MD, Blood Cancers Today Associate Editor, of the University of Texas MD Anderson Cancer Center, focused on the latest data in the treatment of low-risk myelodysplastic syndromes. Dr. Garcia-Manero was joined by Jamie Koprivnikar, MD; George Yaghmour, MD; and Sangeetha Venugopal, MD.
In the next segment of the roundtable series, the panel discusses other treatments undergoing research for MDS, including imetelstat and KER-050.
Watch the next segment in this series.
—
Dr. Garcia-Manero: Let’s start talking about some of the other compounds and interventions. Let’s start with the first one that is imetelstat, a presumed telomerase inhibitor. What are your takes on this IMerge study?
Dr. Yaghmour: Our colleague Amer Zeidan, MBBS, presented at ASCO the data of the IMerge study, randomized control study for patients also refractory or the exposed to erythropoietin-stimulating agent (ESA). The data are very encouraging, and the also response rate and the tolerability of the treatment in low-risk MDS [myelodysplastic syndromes] also made me think from that data now COMMANDS study are moving luspatercept to upfront. Now what about the telomerase inhibitor? If we feel luspatercept is going to be our new practice to switch those patients or should we combine it at some point if they fail? What do you think?
Dr. Koprivnikar: I think the data is really interesting. I do think we haven’t had a good option for patients with a serum EPO [erythropoietin] level greater than 500, but it looks like maybe imetelstat may fill that need. Also sort of response rates across the IPSS-M [Molecular International Prognostic Scoring System] groups tend to be very even regardless of the risk stratification with imetelstat. I thought that that was very interesting.
Dr. Garcia-Manero: Do you have any issues with the degree of neutropenia, thrombocytopenia, and the time it takes for this drug to give you a response? Do you think that’s going to be problematic in the clinic or?
Dr. Koprivnikar: I do think with worsening cytopenias that we may see some difficulties. Certainly that was reported as part of the abstract here. That is a consideration and a concern for some patients.
Dr. Yaghmour: I do agree. I forgot to mention cytopenia might be a challenge, but at the end it’s also the balance and it’s going to be a case by case decision.
Dr. Garcia-Manero: Then the other compound I think of very significant interest, and it tells you how fast things go, is that apparently there is already a second-generation TGF-β modulator, this compound is KER-050. This was presented at this past EHA. What are your takes on this? Do you think that a drug that could have a role? It’s actually quite fascinating, right?
Dr. Koprivnikar: Well, correct me if I’m wrong, but we were just talking about imetelstat having these issues with cytopenias. I believe with this agent we actually saw some platelet responses. I think that’s really interesting. Also some signals that it’s maybe modulating inflammation, some decreasing ferritins. I think this is one of the many very exciting therapies coming down the pike.
Dr. Garcia-Manero: I understand that this drug actually is somehow similar to a compound, sotatercept. It was developing parallel to luspatercept. I’m not sure if you has some type of chemical modification or not, but it is really intriguing that we’ll have a drug working kind of the same pathway. I think at the end these are all good news, right? Because Sangeetha was talking about del(5q)-negative not knowing. But now the reality is that as we develop these drugs and get them approved, we come with kind of new needs. One need is like, “You get this great drug luspatercept, but now you are not responding anymore.” What do I do after that? It’s going to be interesting to see if these drugs will have a place as a second line post-luspatercept, post-ESA, depending on what you do. As you’re saying, should we combine them and maybe understand what is the true molecular context where these drugs work better. Perhaps they are not all the same for all patients with lower-risk MDS. Going back to the molecular heterogeneity that we have.
Dr. Yaghmour: I concur about that. Targeting the activin type II receptor, targeting the Smad pathway and regulator of the inflammatory process that helps in the platelets’ recovery. Honestly from the phase II data that coming this ASH [2023 Annual Meeting] also they’re going to update us about it. It’s exciting and very much a promising additional option and new generation of transforming growth factors pathway inhibitor.