EHA 2019 | Novel approaches for transfusion dependent MDS

Valeria Santini

Valeria Santini, MD, University of Florence, Florence, Italy, discusses transfusion dependency in low-risk myelodysplastic syndrome (MDS) and how this can be targeted. This interview took place at the 24th Congress of the European Hematology Association (EHA) 2019, held in Amsterdam, Netherlands.

Transcript (edited for clarity):

Low risk MDS do not have a high propensity to develop PML or to progress. They may have a very long survival, but the main problem of these kinds of diseases is that they develop, or they have from the beginning transfusion dependency, especially for red blood cells, so they are anemic. The majority of these patients are anemic. Usually they are treated with ESAa, erythropoietic stimulating agents, after different periods of times, but I would say in a couple of years they lose response and when this is done, there are not many alternatives for these patients who become transfusion dependent. There are some drugs that are very promising in this sense. One is Luspatercept that is a ligand trap for active in ligands and blocks the TGF Beta pathway intracellularly. Therefore releasing maturation of erythroid progenitors, especially when the block is a late block as in many MDS.

Now this drug that is given subcutaneous every three weeks has shown a very high success and activity in patients who have an MDS with ring sideroblasts. That means that 37, almost 38% of patients do have a transfusion independency longer than eight weeks after this treatment, which is very good news for patients who receive so many transfusions in a month. And again, the patients who did not become completely transfusion dependent within this phase III study called Medalist (NCT02631070), they do have in 50% of the cases, an improvement, an hematoglogical improvement. So anyway, also possibly an improvement in quality of life. So that’s something that, it’s really supporting the use of this drug for ring sideroblast MDS. There is a study going on this very moment that is comparing ESAs to Luspatercept in patients who have a new diagnosis of transfusion dependent MDS. We will see the results.

Another very important drug, I think, that has to be checked upon and followed is Imetelstat – complete different way, mechanism of action that is, an inhibitor of Telomerase and is a drug that is used IV once a month. The phase II study that has been presented here at EHA shows a 42% overall response rate in terms of a transfusion independence more than eight weeks. But there are groups of patients who have a long duration of transfusion independent more than 24 weeks, that is one third of the total population. So again, this is a phase II, and the phase III randomized trial is going to start. So we possibly will have very new approaches for these low-risk as well and supportive care is improving, but we have to take care that every single patient with a low risk MDS has to be studied very carefully, re-evaluated for presence of somatic mutation, not only at diagnosis, but also when they lose response to any treatment.

So in this case, high and low risk, to decide whether this patient could be one, prompted to receive a transplant or an earlier transplant if they have a mutation that is bringing bad prognosis, or otherwise received target drugs and targeting agents.

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