Nelson J. Chao, MD, MBA: The norm is basically that you start them on steroids, and if they’re progressing within 3 to 4 days, you’d call them refractory. If they don’t get better and don’t get worse, they’re not responding well. Those who progress need to move quickly to something else because they’re not going to do well. Then you have patients who are started on a pretty good dose of steroids, but you can’t taper them. Every time you try to taper, they flare again. These tend to be steroid dependent, which is also a difficult group to treat and probably requires some other line of therapy.

Yi-Bin Chen, MD: Our trials have been a little hindered by grouping all of these patients together, because they’re probably biologically different. But they all have 1 thing in common; they need some other therapy. Hannah, if your patient met some criteria for steroid-refractory lower GI [gastrointestinal] graft-vs-host disease, what’s the treatment algorithm for that patient at your site?

Hannah Choe, MD: Despite FDA [Food and Drug Administration] approval for ruxolitinib [Jakafi], we still enroll to clinical trial if the clinical trial is well designed. Also, in this case, we’ll have the BMT CTN 2002 protocol opening soon. That will be a phase 3 study, which is an inviting option for patients because they’ll be randomized to ruxolitinib vs the investigational product. In this case, the investigational product has some interesting and promising data for grade 3 and 4 acute GVHD, steroid-refractory acute GVHD in particular. That’s an area where we see a significantly lower response rate with ruxolitinib. Using the T-Guard product in BMT CTN 2002 will give us that comparison that we need and that phase 3 level to look at ruxolitinib, which is very quickly becoming the standard of care for corticosteroid refractory disease vs an up and coming promising agent.

If there’s no clinical trial, then we default automatically to ruxolitinib, assuming access and cost isn’t a concern. Otherwise, we’ll fall back on other institutional preferences for drugs, such as alpha-1 antitrypsin, which is great because it has a low infection risk associated with it, but may not be as widely available; ECP [extracorporeal photopheresis], particularly in skin graft-vs-host disease patients; and then tocilizumab [Actemra] in a patient with GI GVHD in particular as well. We also continue to pursue investigator-initiated trials. We have a BET [bromodomain and extra-terminal motif] inhibitor study in phase 1 as well, but these will be used in patients who have received multiple lines of therapy for steroid-refractory GVHD at that point.

Yi-Bin Chen, MD: Yes, you bring up a good point. Off clinical trials, ruxolitinib has probably become the standard of care for steroid-refractory acute graft-vs-host disease based on the trials that Sophie talked about. But there’s still room for improvement. None of us feel like that’s a home run, especially for grade 3 to 4 steroid-refractory disease with lower GI involvement. You brought up some of the ongoing trials. Others include investigating the preservation of intestinal stem cells as an avenue. Others have included the emerging microbiome field and looking at microbiome-directed interventions for this as well. It’s an exciting time for this type of research. There are a lot of trials going on, and hopefully that will ultimately lead to improvement.

Some have postulated that we have failed in the past because we’ve lumped all graft-vs-host disease together when we do clinical trials. We’ve already touched on a couple of points on how we might risk stratify these patients clinically and biologically by biomarkers. In the future, we’re probably going to do what we’re already doing in some of the trials. For low-risk patients, however we define them, we’ll either give them no steroids and an alternative agent—some of those trials are already being done, which have been mentioned—or we might treat them initially with steroids and do a rapid steroid taper because we all acknowledge that we probably overuse steroids with some of these patients. And then for the biologically high-risk patients, I don’t think any of us are comfortable omitting steroids at the moment. For that group, we may do clinical trials doing steroids plus an investigational agent on top of that. Hopefully those new trial designs will ultimately be able to improve outcomes and get us more approvals and translate to better survival for our patients.

Transcript Edited for Clarity