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SOHO 2026 | ESAs, luspatercept, and imetelstat: treatment selection and sequencing in LR-MDS
Valeria Santini, MD, University of Florence, Florence, Italy, discusses treatment sequencing in transfusion-dependent and non-transfusion-dependent lower-risk myelodysplastic syndromes (LR-MDS). Prof. Santini highlights erythropoiesis-stimulating agents (ESAs) as the preferred option for symptomatic, non-transfusion-dependent patients, luspatercept following ESA failure or in selected mildly transfusion-dependent patients, and imetelstat for heavily transfusion-dependent patients or as a later-line therapy following loss of response to luspatercept. This interview took place at the 14th Annual Meeting of the Society of Hematologic Oncology (SOHO 2026) in Houston, TX.
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Transcript
This is a very good point. We can select and we should sequence these treatments. So what I still do in my practice is that I treat patients who are anemic and symptomatic but not transfusion dependent with ESAs. After that, when they lose response, I just have to choose between luspatercept, that is usually the agent that I use and the treatment I implement. And these patients can respond for a long time with transfusion independence and increase of hemoglobin...
This is a very good point. We can select and we should sequence these treatments. So what I still do in my practice is that I treat patients who are anemic and symptomatic but not transfusion dependent with ESAs. After that, when they lose response, I just have to choose between luspatercept, that is usually the agent that I use and the treatment I implement. And these patients can respond for a long time with transfusion independence and increase of hemoglobin. Some of these patients, if they are heavily transfusion-dependent, will not respond so well. So in these very heavily transfusion-dependent patients, then I shift to a second-line therapy with imetelstat. Of course, if the patients will arrive at my office already transfusion dependent, I will immediately start with luspatercept. Again, if not so heavily, more than four units of red blood cells in eight weeks. But what happens if the patient responded for a couple of years or more to luspatercept and then little by little loses response and goes back to transfusion dependence? Imetelstat has shown activity in second and third line, so I will shift to this drug. An important point for the use of imetelstat is that patients with severe thrombocytopenia or neutropenia should not be treated with this drug unless very, very closely followed up, because the drug is similar to what lenalidomide is doing in DEL5Q, is decreasing platelets and neutrophil. But it’s indeed a drug that is IV, that has to be given in hospital, but it’s a drug that has an interesting activity.
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