Future of Acute GvHD Prevention


A look into the future of acute GvHD prevention and discussing the impact of targeting specific organs to help manage GvHD prevention.


Corey Cutler, MD, MPH FRCPC: At ASH [American Society of Hematology annual meeting], there were lots of interesting new concepts. Hannah, what did you think was the most interesting new strategy to come out of ASH in terms of GVHD [graft versus host disease] prevention?

Hannah K. Choe, MD: I don’t know if you can go much farther than the big hit with the BMT CTN 1703 trial. That’s going to obviously be game-changing for everybody here, but there were some interesting new ideas. There were a lot of JAK inhibition combinations that came forward. Are you referring to acute or chronic?

Corey Cutler, MD, MPH FRCPC: Acute.

Doris M. Ponce, MD: There were a lot of interesting preclinical data presented. You can’t talk about GVHD without mentioning T regulatory cells. There were data presented at SOHO [Society of Hematologic Oncology meeting], for example, with the Orca-T trials, with engineering the grafts to have a higher concentration of T-reg cells, seeing promising results from that. There were some preclinical data about the importance of specific T-reg cells in combination, as you mentioned, even the microbiome. T-reg cells have a key relationship with the microbiome that might be important. Also there were some data about infusing T regulatory cells in increasing concentrations and being able to treat GVHD that way as well, which I thought was very exciting.

Corey Cutler, MD, MPH FRCPC: Doris, anything that caught your eye that was particularly interesting in the GVHD prevention space?

Doris M. Ponce, MD: Definitely, the JAK inhibition showing to be safe without affecting engraftment, I thought it was very interesting with the itacitinib data in particular. It could be part of the armamentaria that we could use. We are interested in it for patients with MPN [myeloproliferative neoplasm], that’s something we could incorporate safely into our strategy. JAK inhibition could be used in that setting, and that was interesting for me.

Corey Cutler, MD, MPH FRCPC: Yi-Bin, what about regimens, or strategies that particularly target individual organs? We all know that the impact of GVHD is different depending on which organ is involved, with the GI [gastrointestinal] tract being probably the most important organ in terms of outcomes. Are there any particular strategies you’re interested in that maybe target individual organs?

Yi-Bin Chen, MD: When you speak about acute GVHD, you’re mainly looking at 3 organs, the skin, liver, and the intestines. As all of us know because we take care of a lot of patients, the intestine or the GI tract is the most important. Lower GI acute GVHD causes the most morbidity and mortality for our patients. While we’ve made improvements in the prevention of severe acute GVHD, as evidenced by abstracts presented here already, those patients still hit home. Those are early patients who end up back in the hospital and they sort of demoralize the program. It remains an unmet need, prevention and specific treatment. In terms of organ-specific prevention, we had completed a couple of years ago a phase 3 study that was placebo-controlled randomizing patients to vedolizumab, which is anti–alpha-4 beta-7 monoclonal antibody that targets lymphocyte trafficking to the gut, in conjunction with standard tacrolimus and methotrexate in both myeloablative and reduced-intensity transplants. This is a study that randomized about 340 patients, and we hope to be able to share the results soon to see if there’s a benefit or not. That’s something that’s organ specific, and for the first time, it tries to separate acute GVHD into different organs. If you’re able to make a dent in intestinal GVHD, that’s a victory.

Doris M. Ponce, MD: I have an additional presentation, it’s a multicenter study. [Memorial] Sloan Kettering [Cancer Center] is very vested in the concept. We only presented the clinical trial design, and it’s the use of this ecobiotic capsule. It’s like an FMT [fecal microbiota transplantation] 2.0. It’s basically a beneficial bacteria that is made as a capsule so we know the amount of bacteria, the dosing. These patients are using it in the pretransplant and after-engraftment setting. In our clinical trial design, we’re looking to prove that it’s safe. The efficacy end point includes engraftment of the actual bacteria in the GI tract. One of the secondary end points is prevention of graft versus host disease.

Hannah K. Choe, MD: There are also the preemption trials. The MAGIC study is looking at itacitinib preemption, so it’s not by organ system, but it’s by risk of acute GVHD. It’s measuring high biomarkers or low biomarkers for acute GVHD risk, to be able to see if you can have a steroid-sparing alternative, using itacitinib. That’s not necessarily organ specific but….

Corey Cutler, MD, MPH FRCPC: For those of us who don’t use the biomarkers in routine clinical practice, there was a nice abstract from the CIBMTR [Center for International Blood and Marrow Transplant Research] that looked at an integrated clinical risk score for the development of acute graft versus host disease, which incorporates what most of us think are common risk factors and known risk factors into the development of acute GVHD. It tends to overweigh the conditioning regimen, so we’ll see how this is going to function in a prospective fashion.

Transcript edited for clarity.

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