EHA 2025 | The use of immunosuppressive therapy in MDS: available agents and areas for further research

Yes, in this meeting, EHA 2025, I was asked to give an overview of what are the immunosuppressive therapies. Now, we have been using immunosuppressive approaches in MDS since quite a long time, more than 20 years for sure. But the problem in evaluating the results of these trials and of this approach has been several. First of all, there are really few prospective trials, if any. I think there is only one. And there are many non-randomized trials, single arm. So it’s always difficult to evaluate in the end the results, the outcome of patients. And patients included in the study were indeed heterogeneous in diagnosis. Having said so, there is indeed a signal that immunosuppressive therapy can be very effective in some cases of MDS. Per immunosuppressive therapy, we usually think of ATG or ATG plus cyclosporine or cyclosporine alone, single drug. But we can also include corticosteroids as a very mild immunosuppressive agent. And then we have also another approach, alemtuzumab, the anti-CD52 antibody, or even anti-TNF antibody like etanercept. So I think that overall there have been trials in which there was indeed a good response, especially ATG plus cyclosporine seems to give very good results in terms of transfusion independence. We are looking for biomarkers and we should plan and design prospective trials. So the efficacy of cyclosporine in a single drug in elderly patients can be also more than acceptable with nearly 50% response. Now, the problem of ATG is that it gives side effects and elderly patients cannot be treated like that. Regarding biomarkers driving our choice, we do not have consistent biomarkers. But what has been proposed overall and coming out in many studies in multivariable analysis is that, let’s say an aplastic anemia-like aspect, like hypocellular marrow, the presence of HLA-DR and normal cytogenetics can be considered indeed and age, as I just mentioned, very important. The hypocellular marrow has been confirmed in very many studies, not in all, but it’s still used as a sort of, especially in a couple of studies that came out last year, as a sort of marker of probable and possible response to immunosuppressive therapy. So I think that we should revise and rethink the approach of with immunosuppression in our lower risk MDS patient especially because the alteration in the immune system of MDS changes and is modulated during the progression of the disease from low risk to high risk. So the targets of the treatment may change and we will see also what anti-inflammatory treatment can bring to this field.

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