Frontline Agents for GvHD



Corey Cutler, MD: For prophylaxis of GVHD [graft-vs-host disease], which is required in all cases even with matched donors, there are a couple of accepted standards. At our institution and at most institutions in North America, the accepted combination for prevention of acute GVHD is the combination of a calcineurin inhibitor, typically tacrolimus and less frequently cyclosporine in conjunction with methotrexate. There are some alternative regimens; for example, the combination of tacrolimus with sirolimus, which we use at our institution. And some centers will use the combination of tacrolimus with mycophenolate, particularly in reduced-intensity transplantation, although that regimen is a little less effective. When one starts to go into alternative donor transplantation, regimens like post-transplantation cyclophosphamide is used predominantly in the haploidentical setting and sometimes in the mismatch setting. When we talk about umbilical cord blood transplantation, we typically don’t use methotrexate there, and that’s where regimens like tacrolimus and mycophenolate are used or tacrolimus and sirolimus.

There are a couple of other ways of preventing acute graft-vs-host disease, and some of them involve manipulation of the graft itself. One can either give in vitro or in vivo T-cell depletion where we take the T cells out of the graft or positively select the CD34-positive stem cells and simply infuse those. Most important, we have several clinical trials right now to try to advance the field of GVHD prevention, and really in all instances we do try to enroll our patients on clinical trials to try to advance the field.

Yi-Bin Chen, MD: At our institution, we generally use pharmacological or drug-based graft-vs-host disease prevention, and it generally varies by the type of donor that’s being used. For a fully matched donor, related or unrelated, we still use the traditional backbone of a calcineurin inhibitor such as tacrolimus combined then with small doses of intravenous methotrexate after transplant. The general regimen is tacrolimus started a few days before the transplant orally, followed by intravenous methotrexate given on days 1, 3, 6, and possibly day 11 after transplant.

For transplants we’re using that involve mismatched donors, such as mismatched unrelated donors or haploidentical donors, we’ve adopted the use of post-transplant cyclophosphamide-based regimens. This involves giving an unmanipulated T-cell replete graft on the day of transplant and then coming in on days 3 and 4 with high doses of intravenous cyclophosphamide, usually combined with the use of tacrolimus and mycophenolate on day 5.

Zachariah DeFilipp, MD: At our institution we typically use the traditional combination of tacrolimus and methotrexate for our fully matched transplant. And for patients who are receiving haploidentical transplants or HLA mismatch transplants, we typically use the post-transplant cyclophosphamide approach, in combination with tacrolimus and mycophenolate mofetil.

In the BMT CTN 1203 study that was published in 2019, 3 novel approaches to GVHD prophylaxis were compared in the setting of a phase 2 study. In that study, post-transplant cyclophosphamide was found to have best overall outcomes by being able to improve the GVHD-free, relapse-free survival in patients. Based on that study, there’s an ongoing study being conducted by the BMT CTN [Blood and Marrow Transplant Clinical Trials Network], study 1703, that is going to randomize patients receiving related or unrelated donor transplants to GVHD prophylaxis with either the traditional tacrolimus methotrexate approach or with the post-transplant cyclophosphamide approach. This study is considered by many to be potentially practice changing for our field.

Transcript Edited for Clarity

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