The background of BMT CTN 1703 was really that we were looking to see if we could update the standard of care for graft-versus-host disease prophylaxis. In our field, since the mid-1980s, the standard of care has been a calcineurin inhibitor plus methotrexate, so this was our first and major attempt at a phase III study to see if post-transplant cyclophosphamide, tacrolimus and MMF would best our standard of care in terms of graft-versus-host disease free relapse free survival.

What was the methodology used?

This was a multi-centre study, it was a randomised phase III design. Participants were enrolled one-to-one with the standard of care, which was tacrolimus methotrexate, versus post-transplant cyclophosphamide tacrolimus MMF. All individuals needed to be adults with hematologic malignancies, standard reasons for allogeneic transplantation, standard and acceptable organ function and all participants had to be undergoing reduced intensity conditioning and be receiving peripheral blood stem cell grafts.

What were your findings?

The key result was that post-transplant cyclophosphamide tacrolimus and MMF is indeed superior to tacrolimus methotrexate in graft-versus-host disease free relapse free survival. Specifically, the outcomes of acute and chronic graft-versus-host disease were markedly better in the PTCy arm with no increase in the risk of relapse or progression and no increase in death. So the magnitude of the benefit was really in reducing acute and chronic graft-versus-host disease by about 50%.

What is the impact of these results on clinical practice?

I anticipate that this will change the standard of care in most transplant centres. We now have randomised phase III data showing superiority of post-transplant cyclophosphamide tacrolimus and MMF in terms of reducing acute and chronic graft-versus-host disease. There are, of course, some concerns with this. The more intense immune suppression can be associated with prolonged lymphocyte recovery; it can also be associated with increased risk of infections and we did see that in our study. There was a higher instance of grade 2 infections but, importantly, not a higher incidence of more severe, organ-threatening, grade 3 infections. Nonetheless, some of these results may give pause to some individuals at different centres but overall, with the magnitude of benefit in acute and chronic graft-versus-host disease, I do think that this is likely to transform the standard of care in our field.

Anything else you’d like to add?

I would just like to add that this was an amazing experience, working with 37 different centres across the United States to enrol participants to this important study during one of the most difficult times in our field and as a country. We were enrolling during COVID and this was really a strain on a lot of individuals, a lot of centres. But we still completed the study one year ahead of schedule. This showed how important it was to our community and I am so proud to have worked with this team in getting this done.