Moving Forward in the Management of Acute GvHD - Episode 3
Key opinion leaders discuss treatment goals for frontline therapy in patients with acute graft-vs-host disease.
Corey Cutler, MD, MPH, FRCPC: When you’re starting steroids with a patient who has stage III or stage IV involvement of a given organ, which requires systemic therapy, what’s the goal? Why are you using steroids? Why aren’t you using tacrolimus in that setting?
Usama Gergis, MD, MBA: Most of these patients are already on tacrolimus with therapeutic levels and they had acute GVHD [graft-vs-host disease]. The median times to acute graft-vs-host disease for all comers is about day 40 after transplant. Most patients are on tacrolimus or other prophylactic agents around that time. Historically, steroids have a 50% response rate in acute graft-vs-host disease for all comers. So far, there is nothing better than steroids, so they are unfortunately the necessary evil in this cascade of treatment.
Corey Cutler, MD, MPH, FRCPC: It’s fair to say we’ve tried. The field has done a number of trials of looking at steroids in addition to other agents as frontline therapy for acute graft-vs-host disease. The best example of that was the CTN [Clinical Trials Network] trial led by the group at Johns Hopkins, where steroids plus mycophenolate was tested as initial therapy for acute GVHD and was no better than steroids alone, but there are many other examples of this. Most recently, a very large trial looking at 1 of the JAK inhibitors was halted early because there did not appear to be a significant advantage of the addition of the JAK inhibitor as frontline therapy with steroids, although that data have not been fully released and we haven’t seen all of it, so it’s a little unfair to talk about it right now.
It’s worth mentioning that while we use steroids for the majority of our patients, those patients who have lower-risk or lower-stage acute GVHD might get away without steroids. The trial here to highlight was recently published by Dr Joseph Pidala through the Blood and Marrow Transplant Clinical Trials Network, where individuals who had Minnesota standard-risk, lower-grade acute GVHD were randomized to receive either steroids or sirolimus as monotherapy for their newly diagnosed acute GVHD. These patients had to have lower risk by biomarker assessment according to the Ann Arbor biomarkers, and in this trial, over 100 patients were randomized. The response rates were about 65% to low 70% range without a statistical difference between the subjects that received sirolimus or corticosteroids as their frontline therapy.
There is a subset of patients with lower-risk, favorable-risk acute GVHD who can get away without corticosteroids. This is probably the minority of acute GVHD patients, but there are some. As you mentioned, for the vast majority, steroids at a dose of 2 mg/kg, particularly for people with visceral involvement, is the treatment of choice.
If you do that, how long do you wait? What’s your practical approach to someone with gastrointestinal GVHD who still has diarrhea after 3 or 4 or 7 or 8 days of steroids? What are your triggers to move on to the next line of therapy?
Usama Gergis, MD, MBA: I want to go back to the study that you mentioned. It’s very intriguing.The problem is that the use of acute GVHD markers is not widespread. We do not use these markers, and I would love to be able to find those 20% of patients for whom I can spare the steroids. Do you use markers in your practice?
Corey Cutler, MD, MPH, FRCPC: Only as part of clinical trials. We do not use them as part of routine clinical care at the moment.
Usama Gergis, MD, MBA: Right. It’s pretty intriguing. High-dose steroids so far are the standard of care if we can agree on any standard of care in our practice.
Transcript edited for clarity.