The GVHD Prophylaxis Landscape

Transcript:

Bonnie J. Dirr, APRN: Lastly, before we dive a little bit more into the case with CB [patient with stem cell transplant], this is a collaborative question for both of you surrounding utility of prophylaxis for GVHD [graft-vs-host disease]. Dr Inyang, what are some of the current available therapies for GVHD prophylaxis that are used and eligible for patients with transplants?

Eno-Abasi Inyang, PharmD, BCPS, BCOP: There are many different therapies that can be used for GVHD prophylaxis. Let’s talk [about] a few of them [that are] available. One is abatacept. Another one is a class of medications called calcineurin inhibitors. This consists of tacrolimus and cyclosporine. Sirolimus is a third option. A fourth option is mycophenolate, and then methotrexate, which is pretty common as a fifth option. ATG [antithymocyte globulin] is a sixth option.... The seventh one is the posttransplant cyclophosphamide, which Dr Gooptu pointed to. Really for GVHD prophylaxis regimens, it consists of a combination of the use of calcineurin inhibitors such as tacrolimus and methotrexate [and] was traditionally the most common regimen…. But given more recent data, posttransplant cyclophosphamide really has gained steam, particularly in reduced-intensity regimens. So This regimen with posttransplant cytotoxin usually consists of posttransplant cytotoxin, tacrolimus, and mycophenolate.

Bonnie J. Dirr, APRN: Thank you, Dr Inyang. Dr Gooptu, in practice—and it’s possible Dr Inyang alluded a little bit to this—what is the prophylactic treatment that you treat your patients with the most? And can you walk us through some of the recommendations? You’ve highlighted a bit previously, but the selections that you made for CB in his graft-vs-host disease prophylaxis.

Mahasweta Gooptu, MD: Yeah. So Let me preface this by saying that the last 5 years have probably been the most exciting in the history of GVHD prophylaxis since the original data published by Joe Antin and others on tacrolimus and methotrexate, which remained the standard prophylaxis regimen for both ablative and reduced-intensity transplantation for 4 decades. There was … as Dr Inyang alluded to, [which] has been used in the United States, more widely used in Europe, and has had mixed results in reducing acute GVHD, but consistently seems to reduce chronic GVHD. Unfortunately [it] comes at the risk of higher nonrelapse mortality and in the end, no difference in overall survival, or sometimes a detrimental effect on overall survival. So EtG is not an agent that we use unless we are transplanting a patient for a disease where additional T-cell depletion is required—such as in the benign hematologic disorders where you don’t need a graft-vs-leukemia effect. Sirolimus was and is an amateur inhibitor...the clinical trials were led by some of my colleagues at Dana-Farber, and in a myeloablative study run by the CTN [Clinical Trials Network]. There was no difference in GVHD between tacrolimus and methotrexate and tacrolimus and sirolimus as a combination. Based on that, we don’t typically use sirolimus for prophylaxis for ablative conditioning, particularly if we are using ablative busulfan because there is an increased risk of veno-occlusive disease [VOD]. In the reduced-intensity setting, sirolimus is used more commonly, particularly because the VOD risk is not as high. Then finally, posttransplant cyclophosphamide, which was originally developed by the [Johns] Hopkins Group for effectively doing transplants with haploidentical donors but has made its way to the mismatched unrelated donor setting and to the fully matched unrelated donor setting because of its excellent results in the haploidentical setting. A few weeks ago, we published in the New England Journal [of Medicine] the results of a randomized trial, comparing posttransplant cyclophosphamide along with tacrolimus and mycophenolate vs the standard of care, tacrolimus and methotrexate. The results were superior with the posttransplant cyclophosphamide regimen in terms of GVHD-free relapse, free survival, and severe forms of acute and chronic GVHD. Based on that, we have changed our practice in the last few months where all our reduced-intensity transplants are done now with a PT-Cy (posttransplant cyclophosphamide)-based regimen with either tacrolimus or sirolimus along with MMF (mycophenolate mofetil). In the ablative setting, the field is still a little bit in flux. Dr Inyang mentioned abatacept, which is a checkpoint inhibitor which ultimately suppresses T-cell activity and was developed by Dr Leslie Kean and others at Boston Children’s [Hospital]. It is the first drug approved by the FDA for GVHD prophylaxis. Interestingly, tacrolimus was never approved. The combination of abatacept to tacrolimus and methotrexate was superior to the standard of care tacrolimus and methotrexate in a randomized [phase 2] trial called the ABA2 trial [NCT01743131]. I will say that we have not adopted it as much as perhaps we could for many different reasons, and parallelly, the data from a CTL trial also showed that PT-Cy is better at GVHD prophylaxis with no difference in overall survival with tacrolimus and methotrexate. Some of us will use PT-Cy in high-risk patients where we think they are high risk for developing GVHD or if we are using peripheral blood stem cells. When they used tacrolimus and methotrexate in the ablative setting, we tried to use marrow product because it’s one of the strongest factors which influenced the development of chronic GVHD. But more to come in the ablative space, I think, in the next few years, really cementing what the standard of care would be.

Transcript is AI-generated and edited for clarity and readability.