Updates in the Management of Graft-Versus-Host Disease - Episode 6
Corey S. Cutler, MD, MPH, FRCPC: Dr Chen, can you elaborate on clinical trials these days and what we’re trying to do in graft-vs-host disease [GVHD] prevention?
Yi-Bin Chen, MD: The last few years we’ve seen a resurgence in investigation into improving the prevention of graft-vs-host disease. There are 2 ways we’re embarking on this investigation. The first is trying to debunk that traditional backbone of calcineurin inhibitor with methotrexate, and the second is to add an agent to make it better. The first is currently being decided by clinical trials being done to the BMT CTN [Blood Marrow Transplant Clinical Trials Network]. There are 3 in the series of PROGRESS studies.
PROGRESS I was a phase 2 study looking at reduced-intensity transplant that randomized patients to 3 different regimens. Two of them were adding an agent onto a tacrolimus methotrexate backbone, 1 using bortezomib, 1 using maraviroc. The third was what Joe mentioned, a PTCy, or post-transplant cyclophosphamide–based regimen. This was all in conventionally matched transplants. These regimens weren’t compared with one another, but they were each compared with a control from the CIBMTR [Center for International Blood and Marrow Transplant Research] contemporaneously receiving tacrolimus methotrexate.
The only arm that appeared to have some benefit or being superior in the composite end point of graft-vs-host disease relapse-free survival was the post-transplant cyclophosphamide arm. Based on the results of that study, the PROGRESS I study has led to the PROGRESS III study, which is an ongoing phase 3 study comparing PTCy with standard tacrolimus methotrexate. Accrual is ongoing at the moment, and we await the results. In the myeloablative setting, the PROGRESS II study was conducted, and accrual has been finished. This was in myeloablative transplants in a phase 3 study comparing tacrolimus methotrexate with post-transplant Cytoxan alone with ex vivo T-cell depletion through a column.
We eagerly await those results too. Both of those studies have the potential to redefine what the prophylaxis of graft-vs-host disease is moving forward. There are also a slew of studies that I mentioned that are adding agents onto the standard tacrolimus methotrexate or calcineurin inhibitor backbone. These were led recently by adding what Zach [DeFilipp] mentioned, which was the antithymocyte globulin, or ATG, products. There have been interesting results from several phase 3 studies along those lines.
Other agents that are ongoing or have been recently done, including the monoclonal antibody vedolizumab and the protease inhibitor alpha-1 antitrypsin. Joe [Antin] mentioned the costimulatory blockade agent abatacept. There is more research going on to CCR5 blockade in addition to maraviroc. The JAK inhibitors that we’ll talk about soon are entering the prophylaxis realm as well. There are manipulations of the microbiome that many of us are interested in that are being studied for GVHD prophylaxis.
The IL-6 blocker tocilizumab has been studied. Two recent abstracts recently presented interesting targets of CD24 and CD26 that are being taken to larger studies as well. It’s a very busy field, which is good, and we all look forward to participating in these studies and seeing the results to see if we can improve on the prevention of graft-vs-host disease.
Corey S. Cutler, MD, MPH, FRCPC: Excellent. There’s lots of activity in the pharmacological sphere. Lots of groups are evaluating strategies that manipulate the graft itself to try to prevent graft-vs-host disease, either strategies that remove all or selectively remove T cells from the graft. There are some strategies that manipulate the graft in vitro either with pharmacological agents given in the bag or in the lab before the cells are given, and some very interesting suicide gene approaches are being done. The entire field of graph emulation, which we shouldn’t ignore, is done only at a select few centers in North America now.
Transcript Edited for Clarity