EBMT 2025 | Stratifying patients with MDS to optimize outcomes of alloSCT

We will discuss today what we can do to improve the outcome of patients with MDS undergoing transplant. And one of the most important things is that we have to take into account the newest, I would say they are no longer new because they are almost three years old, way of prognostically stratifying MDS patients. One indeed very important tool is to use the IPSS-M, therefore to integrate clinical and NGS, somatic mutation data of patients to establish the prognostic risk. And there is this part, so indeed including this evaluation in the timing, the decision in timing of transplant, which is different for, of course, low-risk MDS and high-risk MDS. So the patients with low-risk MDS would take advantage in waiting and having a delayed transplant, whereas the higher-risk MDS patients, and I’m talking about IPSS-M risk, no longer of IPSS-R, then the higher risk MDS patients will take advantage in early transplant. And this is mainly interesting and important for the younger patients. So the older patients will have a higher risk. And again, the advantage in terms of life expectancy, prolonged life expectancy, it’s a little bit different. So we have to take into account age, state and risk of the disease as much as we always did comorbidities. And you know, the importance of these findings and observation is increasing because we do not have yet a good therapy that is improving the results we have with azacitidine alone as a bridge to transplant or as therapy by itself. Several combinations have been attempted to improve the survival rate and the response in high-risk MDS. But unfortunately, until now, we do not have any new therapy to propose to our patients. We are waiting for the results of the combination of azacitidine plus venetoclax in the Verona trial, but we do not know whether there will be soon a display of the results. We hope so. But in the meanwhile, the only cure we can propose to our patients who are eligible is transplant, hematopoietic stem cell transplant. Therefore, this is why I stress the importance of stratifying prognostically as in the best way as possible our patients. So if we have a molecular testing, this may indeed improve our timing. So clinical and molecular data together will certainly help us to decide when and how to transplant the patients for their optimal outcome. Regarding lower risk MDS. Again, IPSS-M can help us, not so much in transplant, but also in deciding the therapy. There are several options of therapy now. None of them is curative, but what we may have is transfusion independence by scheduling and sequentially proposing to our patients who are transfusion dependent for red blood cells, luspatercept, and first of all, EPO, luspatercept, and then imetelstat. And regarding this last therapy that has a completely different mechanism of action from the previous ones, I just want to add that it has disease-modifying effects. And this is quite important. together with mild and transient myelosuppressive effect, imetelstat can decrease the variant allele frequency of several somatic mutations, indicating possibly that this drug is acting on the myelodysplastic clone. So we have on one side EPO and luspatercept, who may increase and stimulate erythropoiesis, and then another drug that stimulates erythropoiesis but also possibly decrease the size of the dysplastic clone. Then in some cases, although I said it’s not the first choice, some patients with low intermediate type IPSS-M risk should be considered for a transplant. So I think that the tools and weapons. I don’t like this word anyway, but the tools we have to improve survival in our patients with MDS is increasing and we really hope to be able to cure more and more patients in the future with a very careful approach to transplant and to the choice of therapy.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.