The Potential for Post-transplant Cyclophosphamide for GVHD

Yi-Bin A. Chen, MD:Post-transplant cyclophosphamide has been a major development in transplantation over the last 2 decades. First developed by our colleagues at Johns Hopkins Medicine, it was first publicized in the use of haploidentical transplantation. It has actually made haploidentical transplantation safe and really almost the standard of care for a variety of transplant indications.

The ability to engender engraftment and successfully prevent acute and chronic graft-vs-host disease [GVHD] is remarkable. And so it was only natural, after seeing the success in haploidentical transplantation, that we all thought about studying post-transplantation in the more conventional donor space—that being either matched related or matched unrelated donors.

At our center, we generally have used post-transplant cyclophosphamide-based graft-vs-host disease prevention for our haploidentical transplants. We have now used it as our standard for patients who are receiving mismatched unrelated transplants as well. Recent results have suggested that we should now consider post-transplant cyclophosphamide for use for our standard patients as well.

These results include the now-published trial of BMT CTN 1203. This was a reduced-intensity trial. This was a trial of reduced-intensity transplants that compared 3 different graft-vs-host disease prevention regimens with a registry control of our standard of tacrolimus with methotrexate. The results of this trial suggested that post-transplant cyclophosphamide-based GVHD prevention was superior in that comparison. Now the BMT CTN is moving on to a formal phase III, prospective trial comparing our standard of tacrolimus-methotrexate with post-transplant Cytoxan [cyclophosphamide] in the reduced-intensity platform.

At the 2019 ASH [American Society of Hematology Annual Meeting & Exposition], 1 of the abstracts in the plenary session was on a similar study in reduced-intensity transplants comparing post-transplant cyclophosphamide-based graft-vs-host disease prevention with a standard of cyclosporine with mycophenolate mofetil.

The results of the trial were to be presented showing that patients who receive post-transplant cyclophosphamide-based graft-vs-host disease prevention had a clear benefit in reductions in severe acute graft-vs-host disease, moderate to severe chronic graft-vs-host disease, and the composite end point of graft-vs-host disease—relapse-free survival. Those results are compelling. We await results of this phase III study by the BMT CTN.

Our group at Massachusetts General Hospital also presented an abstract at this ASH meeting showing the results of 9 patients with nonmalignant hematologic disease such as aplastic anemia, Diamond-Blackfan, as well as pure red cell aplasia who underwent allogeneic transplantation using a post-transplant cyclophosphamide-based platform. We had read the results published by our colleagues at Johns Hopkins showing such success in haploidentical transplants and conventional donor transplants, and their results using this platform for nonmalignant hematologic disease.

Several years ago we had adopted this, and it appeared to be our most potent way of preventing graft-vs-host disease for this specific population of patients who have 0 benefit. Our results presented at ASH on our 9 patients treated over the last 5 years are very compelling, showing all patients with full donor hematopoiesis and very little graft-vs-host disease and all patients surviving. Those past 12 months were all off systemic immunosuppression, and now this has become our standard for this population of patients.

Transcript edited for clarity.