EHA 2025 | ALLG BM12 CAST: post-transplant cyclophosphamide for GvHD prophylaxis in stem cell transplantation

This is a randomized study which is unusual. Not a lot of randomized studies in allogeneic stem cell transplantation. So the area of focus for this trial was to look at a better way to prevent graft-versus-host disease. So transplants are done to cure high-risk blood cancers but unfortunately about a third to a half of people still develop graft-versus-host disease despite our current prophylaxis. And so the current prophylaxis is a combination of a calcineurin inhibitor and an anti-metabolite. So in Australia it’s cyclosporine and methotrexate. And some people or centers add in antithymocyte globulin but that’s a little controversial so many of the US states don’t use it, while European and Australian states often do. So anyway, this trial was to ask the question whether post-transplant cyclophosphamide would be better than the standard of care. And essentially, the trial was a randomization, one to one, 134 patients who were transplanted using just a matched sibling transplant, so not unrelated or haplo. And they were transplanted for high-risk blood cancers, so acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplasia. And the primary endpoint was graft-versus-host relapse-free survival. So that’s people who have not developed significant graft-versus-host disease. That was defined as grade 3-4 acute and moderate to severe chronic graft-versus-host disease. They hadn’t relapsed and they were still alive. And the two arms were standard of care, which was cyclosporine and methotrexate, compared with post-transplant cyclophosphamide plus cyclosporine, so no anti-metabolite, which is one of the unusual things about this trial to be able to avoid methotrexate or mycophenolate. So we followed the patients for about three years in total. And the people that got the standard of care, only 14% after three years remained alive, free of disease and had not suffered any significant graft-versus-host disease. While in the experimental arm, receiving the cyclophosphamide, cyclosporine, almost half, so 49%, remained alive without disease and had not suffered any significant graft-versus-host disease. So that’s a threefold improvement in the chances of having a successful transplant. So I think that this is a really important trial because it not only adds to the previous randomized trials, so there’s been two main randomized trials looking at this sort of question. The things that are different from ours is one, there’s no mycophenolate. And I think that is the reason we saw very little toxicity so there was no increased toxicity, no in fact less deaths which correlated with improved relapse-free survival. The other important thing was that it included younger patients receiving myeloablative conditioning so all the other studies have been restricted to older patients receiving reduced intensity so this is a much broader applicability. And I think this study probably is sort of the nail in the coffin for the traditional prophylaxis that still is used. And hopefully that when people see this data, they’ll be convinced that it is an effective, more effective strategy, safe and can be used for basically all patients having a sibling, matched sibling donor transplant.

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