The question today is about whether ATG remains the standard of care for GvHD prophylaxis, or post-transplant cyclophosphamide is going to take over. I think we have a lot of data, retrospective studies, registry-based studies, Phase II trials, Phase III randomized trials, demonstrating that ATG is clearly a powerful tool for GvHD prophylaxis prior to allotransplant, and it is recommended when it comes to matched unrelated donors based on the Phase III randomized trials...
The question today is about whether ATG remains the standard of care for GvHD prophylaxis, or post-transplant cyclophosphamide is going to take over. I think we have a lot of data, retrospective studies, registry-based studies, Phase II trials, Phase III randomized trials, demonstrating that ATG is clearly a powerful tool for GvHD prophylaxis prior to allotransplant, and it is recommended when it comes to matched unrelated donors based on the Phase III randomized trials. We also know that this is also true in both in the myeloablative conditioning setting, and in the reduced-intensity conditioning setting.
More recently, we’ve seen the event of high-dose post-transplant cyclophosphamide, thanks to the great work from the John Hopkins group, and post-Cy, let’s call it post-Cy, proved to be extremely powerful and feasible in the haploidentical transplant setting for GvHD prophylaxis. And this has allowed actually, the wide spread and expansion of the use of haplo donor, and this has been really a huge achievement in the field of allo-transplant.
Now, the question of course is, if post-Cy is a good treatment option, good GvHD prophylaxis in the haplo setting, why can’t we use it in other transplant setting? It’s not an easy question, and the answer is not straightforward. For instance, when you look to the registry data, obviously results are not always the same from different sources. When it comes to the mismatched donor’s allo-transplant setting, like nine out of 10, we have data from the registry showing that probably post-Cy is doing better than ATG. You have also data showing that the results are the same when it comes to matched unrelated donors or siblings.
So, lots of controversies there. We may be able to solve this from a randomized trial. And we had such trial, Phase II randomized trial, focusing exclusively on a reduced-intensity conditioning setting and the first results were presented at the EBMT 2021 virtual meeting, showing that actually when you use backbone conditioning with fludarabine IV busulfan, plus ATG for GvHD prophylaxis, or post-transplant cyclophosphamide, actually, the results are the same when it comes to the main outcome, namely, acute GvHD incidence, chronic GvHD incidence, but also disease-free survival. And most importantly, transplant-related mortality, or non-relapse mortality. So, you can appreciate, I think post-transplant cyclophosphamide is definitely a major breakthrough in our field, but still, ATG remains a very well-established treatment modality for GvHD prophylaxis.
So, this is really very exciting and I think we really need to continue and dig deeper into these different transplant settings to figure out what would be the optimal GvHD prophylaxis and maybe the solution will come from actually combining both ATG and post-transplant cyclophosphamide, as we have published this in different series, especially if you are using peripheral blood stem cells. So, this is really going to be very exciting, and we’ll have a lot to do for the next few years.
