Scenario 1: Selecting Therapy for Acute Graft-Versus-Host Disease
A panel of experts discuss systemic therapy to manage a patient with acute graft-versus-host disease.
Transcript:
Nelson Chao, MD: We we will talk a little bit more about gradient staging in a minute, but Corey, what would be your immediate treatment plan for this patient?
Corey Cutler, MD, MPH, FRCPC: So this person has multiorgan involvement, including visceral organs of the liver and the gut. So this is the type of person who I would initiate therapy with systemic corticosteroids as the main stay. In general, my approach is [a] dose of 2 mg/kg because both liver and the gut are involved. Either 1 of those would make me want to use that dose. I sometimes start with a lower dose when skin only is involved, and every now and then we can get away based on some data from clinical trials that work off just using sirolimus [Rapamune] if low-risk skin disease is present alone. But here I would start with steroids 2 mg/kg and I would consider all the ancillary things that we know have to go along with corticosteroid therapy for patients with acute GVHD [graft-versus-host disease]. So very close monitoring of blood glucose and very close attention to things like osteoporosis in the long term are crucial. Even considering to start things like a bisphosphonate at the initiation of corticosteroid therapy, or gastrointestinal protection with a H2 blocker or a proton pump inhibitor are important to minimize the potential side effects of corticosteroids.
Nelson Chao, MD: Great. In addition, firstly, all of the patients already are in their PKP and in that fumble mental block profile access. This would also be very important to be sure we don’t forget those. So she got started 1 mg/kg on topical steroids. After 3 days there was no treatment response, so the dose was increased to 2 [mg/kg]. Five more days after that, the rash showed really no significant improvement. When I look at what to do next, how do you define starting acute GVHD? I think it’s pretty clear when they don’t respond within 3 days or they don’t get better after 7. I think most of us would consider this to be refractory. I think we are going to switch it over to see what the best treatment would be now for somebody who has refractory acute GVHD. I think the most important thing is to remember that there are global trials still ongoing. Even though we do have an FDA [Food and Drug Administration] approved drug, I think there is still room for improvement. The approved drug is ruxolitinib [Jakafi], and that is the only approved drug. There are lots of other drugs out there that people have used like alemtuzumab, basiliximab, other calcineurin inhibitors, etanercept [Enbrel], ECP [extracorporeal photopheresis], infliximab [Remicade], and so forth. Many of these do have response, but none of these have undergone a phase 3 randomized reach studies for the treatment of acute GVHD. So the standard care for us would be to go on a clinical trial. It’s one of their rules. If not, it will be ruxolitinib that covers it.
Corey Cutler, MD, MPH, FRCPC: I completely agree. We all have our own in-house preferences in terms of what the agent would have been before we had the randomized reach studies. But now we do have an FDA approved agent that has been demonstrated to be superior to our own best choices or best guesses in that setting. We also would do a clinical trial at this point or the standard of ruxolitinib when a trial was not available.
Nelson Chao, MD: Ms Minor, what are some of the things besides infection and prevention we should worry about at this point for some of these patients at steroid-refractory phase?
Kerry King Minor, MSN, ANP-BC: At this point, you just might not feel comfortable stopping steroids. Now they have been on them for a while and until you get something on board that starts to take control of the sentence, you are going to continue on the steroids to some degree. So, I start to worry about the biggest things, which, from the initial portion of the transplant, is steroid myopathy. Taking cell or getting physical therapy and occupational therapy involved and not letting it go too long to the point where nutrition is an issue. So we want to make sure [a] nutritionist gets involved. Consider some other source of nutrition if they are starting to lose weight and support them from that side of things as well. Those are probably the 2 biggest things. Looking at what Dr Cutler said, it is important to look at PSAs with high glucose and making sure that we get the endocrinologist team involved as well. Kind of pulling in all the different disciplines to support them.
Transcript edited for clarity.
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