Overview of Steroid-Refractory Chronic GvHD

EP: 1.Diagnosis of Chronic GvHD

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EP: 2.Overview of Steroid-Refractory Chronic GvHD

EP: 3.Switching Therapies in Steroid-Refractory Chronic GvHD

EP: 4.Treatment Options for Steroid-Refractory Chronic GvHD

EP: 5.Sequencing Therapies in Steroid-Refractory Chronic GVHD

EP: 6.REACH3 Trial in Steroid-Refractory Chronic GVHD

EP: 7.Clinical Implications from REACH3 in Steroid-Refractory Chronic GVHD

EP: 8.Future Directions for the Treatment of GvHD

EP: 9.Recap: Earlier Detection May Be Key to Treatment Advances in Chronic GVHD

Matt Fowler: How often do you encounter patients with steroid-refractory chronic GvHD [graft-versus-host disease] in your specific practice?

Yi-Bin Chen, MD: I’ll take a step back and think about the incidence of steroid-refractory chronic graft-versus-host disease in my practice. First, you have to think about what percentage of patients develop chronic graft-versus-host disease. I bet if we looked hard enough, we would see that 70% to 80% of our patients develop some symptom of chronic graft-versus-host disease. Now, a lot of these patients would just have isolated ocular or oral involvement that requires some topical therapy, and probably only about half of those require systemic therapy. These are usually the patients we think about when we’re trying to improve outcomes, and certainly improve systemic therapy. Probably about 40% of patients who undergo transplant at my institution will develop some chronic graft-versus-host disease that requires us to institute some systemic therapy. Long-term studies would suggest that probably half of those patients would qualify as either steroid-dependent or steroid-refractory, thus necessitating us to use a second-line agent. Probably about 20% of our population that we transplant will at some point in their long-term follow-up require a second-line agent for chronic graft-versus-host disease.

Matt Fowler: How do you define this disease in your practice, and can definitions vary across clinical practices?

Yi-Bin Chen, MD: The definition of chronic graft-versus-host disease has been debated through the years. Part of it is because of what we talked about before, which is that judging the activity or the response in chronic graft-versus-host disease is difficult to begin with and inherently subjective. The way I practically define it is that I will start systemic steroids, and I will wait at least a month before making a real judgment. Now, there are some patients in that month who will truly get worse. That’s obvious. Looking at assessments like liver function tests is easy because they are numerical, but a lot of the other assessments are based on physical examinations and symptoms, and those are a little more difficult to figure out, but I try to give steroids at least a month to work. If patients are not improving after 1 month of therapy on systemic steroids, I would call them steroid-refractory, practically. In clinical trials, we’ve also lumped the steroid-dependent population into this group. What that means is patients may have a response to steroids, but it’s definitely not a satisfactory response. When you taper the steroids, because steroids have morbidity that we all understand, what you see is that as you lower the dose to a certain threshold, their symptoms or manifestations of chronic graft-versus-host disease may flare or come back. Those patients qualify as steroid-dependent. They also fit into the big umbrella definition of steroid-refractory when used in clinical trials. Those are the main practical definitions for me.

I will admit that there are some patients who I don’t even start on systemic steroids for chronic graft-versus-host disease because of 1 reason or the other. The 2 main reasons are either they have manifestations that, just clinical experience-wise, I know they won’t respond, or they have such significant morbidities such as brittle diabetes or severe osteoporosis, or they’ve had psychosis on steroids before, where it is clearly the wrong treatment. For those patients, I guess I wouldn’t call them steroid-refractory, but they definitely require another line of therapy beyond steroids.

Matt Fowler: I think you started to touch on this briefly, but could you expand on what some of the clinical challenges are in identifying patients with steroid-refractory disease?

Yi-Bin Chen, MD: Identifying patients with steroid-refractory chronic graft-versus-host disease can be challenging. As I said, there’s a subset of patients who clearly don’t respond and are getting worse, so that’s easy. There’s a subset of patients who get better, so that’s easy too. It’s the patients in the middle who aren’t obvious, and sometimes it’s difficult to figure out if they’re truly steroid-refractory or not. Again, part of this is because chronic graft-versus-host disease is clinical, and we usually don’t have a number, a metric, a laboratory test, or a biomarker that tells us how the activity is. These patients often have significant comorbidities from just life in general, but more often from the treatments they’ve undergone to get to that point. Teasing out symptoms from chronic graft-versus-host disease or other comorbidities can be challenging and difficult. Is the leg pain from the scleroderma, or is it from their preexisting peripheral vascular disease? Trying to figure those things out can be difficult, and it’s critical because we don’t want to start additional treatment on patients who may not need it. At the same time, we don’t want to leave patients on steroids and dependent on the steroids for an extended period because of the morbidity that those steroids may cause. It’s in this subset where they don’t have a clear clinical benefit and where they’re clearly not getting worse, where we’re trying to figure out if we should add a second-line agent or not.

Transcripti Edited for Clarity