Advances in the Management of Graft Versus Host Disease - Episode 4
Sophie Paczesny, MD, PhD; Yi-Bin Chen, MD; and Hannah Choe, MD, review recent advances in GVHD prophylaxis as presented at the 2021 American Society of Hematology (ASH) Annual Meeting and Symposium.
Yi-Bin Chen, MD: I want to touch on 2 abstracts presented at the American Society of Hematology Annual Meeting that involved graft-vs-host disease [GVHD] prevention. The first was research done by a company called Orca Bio that was working with our colleagues at Stanford University and a few other centers on the West Coast. They presented a clinical trial in myeloablative transplantation using their proprietary product Orca-T, which is a novel graft manipulation strategy. Sophie, do want to talk about that abstract a little?
Sophie Paczesny, MD, PhD: Yes. This is using regulatory T cells [Tregs]. I’m a firm believer in regulatory T cells. They’re absolutely essential to regulate GVHD after transplant. There’s basically a 1:10 ratio of regulatory T cells to effector T cells. You can transfer these Tregs, this graft, as a prophylaxis to avoid GVHD, because they’re depleted after bone marrow transplantation, and people who develop GVHD will have fewer Tregs in general. The outcomes were interesting. They were used as prophylaxis in this case. We had really good outcomes: low GVHD, low acute GVHD, low chronic GVHD, and no difference in relapse rate, which is always the risk when you add prophylaxis, that you decrease the graft-vs-leukemia. This wasn’t the case in their study. We need something to look forward. This was a combination phase 1/2 study.
Yi-Bin Chen, MD: Yes, and they’re making plans to move to a phase 3 study to apply for regulatory approval, which will hopefully get started soon. The second abstract was done by our colleagues at the NIH [National Institutes of Health]. You heard Dr Nelson Chao mention the emergence of post-transplant high-dose cyclophosphamide [Cytoxan]–based regimens. This regimen was developed by colleagues at Johns Hopkins University giving cyclophosphamide at 50 mg/kg per day on days 3 and 4 after a T-cell–replete graft. This abstract asked the question, do we really need that much Cytoxan? Because high-dose Cytoxan is not without risks and toxicities.
It was a dose de-escalation study that treated patients at several dose levels, settling on 25 mg/kg per day as their ideal dosage that still engendered engraftment and protected against graft-vs-host disease. It’s interesting, although it was a small number of patients, and we’ll need to see the expansion. Hannah, do you think we need to refine high-dose cyclophosphamide after transplantation?
Hannah Choe, MD: I thought that was a great study for that exact reason, because some of the limitations of post-transplant cyclophosphamide are the chemotherapy toxicities related to cardiac fluid overload. By dose reducing, we can see a decrease in that, making it a more viable option for more patients. What will be interesting to see long term out of those data is if the concern for CMV [cytomegalovirus] reactivation or viral reactivation at the lower dose is also improved over time. Certainly, if we’re able to maintain great efficacy as far as acute GVHD prevention with a lower dose, and reduce toxicity, that’s absolutely the way to go. I’m very excited about those data.
Sophie Paczesny, MD, PhD: I’ve seen the data. Biologically, they seem even better than the higher dose. You have better Tregs expansion and fewer T effectors. This was in a reduced-intensity setting. I also want to mention that an Italian group has also tried days 3 and 5 recently in the full-intensity setting also with reduced toxicity, which is interesting. There will be adjustment for cyclophosphamide post-transplant.
Transcript Edited for Clarity