Post-Transplantation Cyclophosphamide, Tacrolimus, Mycophenolate and Mofetil vs Standard Prophylaxis for Patients With GVHD

Javier Bolaños Meade, MD, KHS, Johns Hopkins University School of Medicine, Baltimore, Maryland, shares data from a phase 3 trial on post-transplantation cyclophosphamide, tacrolimus, mycophenolate and mofetil prophylaxis vs a standard prophylaxis of tacrolimus and methotrexate for patients with graft-versus-host-disease (GVHD). 

The findings of the trial, Bolaños Meade explains, suggests that the experimental prophylaxis offers better results than the standard prophylaxis, suggesting that this may be the preferred prophylaxis strategy for certain patients. 

Transcript:

Hello, my name is Javier Bolaños Meade. I'm a professor of oncology at Johns Hopkins University School of Medicine, and I'm going to talk to you briefly about the results of our most recent study, BMT CTN 1703. 

BMT CTN 1703 was a randomized phase 3 study comparing 2 [types of] graft-versus-host disease prophylaxis. In 1 part we have the classic standard [of] methotrexate and tacrolimus, which was compared to the experimental arm consisting of post-transplant cyclophosphamide, mycophenolate, mofetil, and tacrolimus. The idea of the study was obviously to see which arm was more effective.

We had a combined endpoint, so the idea was not just to see if one or the other was more effective at preventing graft-versus-host disease, but to see if one was more effective at preventing graft-versus-host disease and giving better outcomes for patients. In order for the patient to be considered a success, [they] needed to be free of severe graft-versus-host disease, grades 3 and 4; [they] needed to be free of chronic graft-versus-host disease requiring immunosuppression; [they] needed to be alive, and they needed to be in remission. All these elements were considered a positive outcome for the patient. 

As I mentioned, patients were randomly assigned to one strategy or the other, and they were followed for 1 year, the minimum, and the primary endpoint was assessed at 1 year. What we observed is that about 52% of the patients assigned to the cyclophosphamide arm achieved the primary endpoint, compared to about 34% of the patients receiving tacrolimus and methotrexate. This difference was statistically significant. And so again, patients were in remission, were alive, and were free of severe graft-versus-host disease acute or free of chronic graft-versus-host disease requiring immunosuppression. 

The interesting thing is that these results were obtained without seeing [an] increase in relapse, as usually when graft-versus-host disease control is obtained, the patients are usually at higher risk for relapse. We did not see that. We saw that patients did better, and they were not punished with an increased risk of relapse. Also, we observed that there was no substantial difference in other outcomes such as graft-versus-host disease, acute or chronic, or more severe infections. That is essentially what the study was about.

The findings of this study, which are applicable to patients receiving reduced intensity condition transplants, essentially suggests that the use of post-transplantation cyclophosphamide, mycophenolate, mofetil, and tacrolimus offer better results than, in the past, tacrolimus and methotrexate will offer, and suggest that this is the preferred prophylaxis strategy to be used on patients receiving these type of transplants. 

The study included only adult patients, so that's something to keep in mind. And the medium age of the patients enrolled in the study was 66—that suggest that patients even of advanced age will benefit from this strategy. Thank you very much.

Source:

Bolaños-Meade J, Hamadani M, Wu J, et al. Post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis. N Engl J Med. 2023;388(25):2338-2348. doi: 10.1056/nejmoa2215943