Advances in the Management of Graft Versus Host Disease - Episode 15

Unmet Needs in GVHD Management

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Drs Sophie Paczesny, Hannah Choe, Nelson J. Chao, and Yi-Bin Chen share unmet needs in GVHD and advice for disease management.

Yi-Bin Chen, MD: We’ve touched on variety of topics in acute and chronic graft-vs-host disease [GVHD], from diagnosis to management. We’ve touched on the most recent trials and the new approvals that we thankfully have at our disposal to help our patients. But that doesn’t mean we’re satisfied. There’s definitely more work to be done. We’re going to go to go down the line here. Sophie, can you sum up where you think the greatest unmet needs in GVHD remain?

Sophie Paczesny, MD, PhD: First, I want to say kudos to the field. A lot of new drugs are approved, so that’s positive. We still need to have 40% of patients taken care of beyond these new drugs. We don’t involve biomarkers enough at each center. We should really do it…for chronic GVHD. It’s not easy to have 1 investigator doing that; it needs to be a consortium. That’s where we can improve on biomarkers. Also, we don’t talk enough about the cost for the patient. We need to have FDA approval but also be sure that everything is reimbursed. We’re in the United States, where these are accessible drugs, but sometimes I give talks to countries outside Europe and the United States, and it’s difficult access for them. Sometimes corticosteroids are still an interest if it’s added with some biomarkers or some drugs, but targeted. We need to have biology. That’s where we can improve. Biomarkers, costs, and new targets that are more specific for the biology.

Yi-Bin Chen, MD: Nelson?

Nelson J. Chao, MD, MBA: I couldn’t have said it better. There are 2 areas where there has been a lot of work done. One is endothelial cell injury, which we didn’t talk much about. Protecting endothelium may have an important impact in GVHD. The other, as you mentioned, is the gut microbiome or the skin microbiome. There’s still lots to learn there. As Sophie was mentioning, understanding the biology is still important. The greatest unmet need is patients who still breakthrough steroids. We do much better—we have these drugs, but if you follow these patients long enough, the percentage of long-term responders is much less than those initial responses. People still progress. That’s a problem.

Yi-Bin Chen, MD: Hannah?

Hannah Choe, MD: As we discussed before, we’re trying to identify the subset of patients who can be defined as lower risk and eligible for noncorticosteroid therapy. We can expect a higher response rate in that category and avoid corticosteroids entirely. Defining that, whether it’s by biomarkers or clinical risk scores, is something that will naturally happen as we use these drugs more in the future, gain more experience with them, and become more comfortable using them in the front line.

I agree with Nelson regarding those corticosteroid-refractory patients. How do we better treat them? How do we essentially protect their GI [gastrointestinal] tract? How do we improve their response by protecting against cell injury in addition to ruxolitinib, for example? There are ongoing trials looking at apraglutide in addition to ruxolitinib. Those will be really interesting data in the next years.

Yi-Bin Chen, MD: I agree with you all in terms of risk stratification and reliable, validated methods that are rooted in biology yet still easy to use to be able to conduct trials. I agree with Nelson. Even though a very small minority of patients get severe acute GI GVHD—the steroid-refractory type—and perhaps die from it, they stick with us. Those are the crushing ones, when we take care of patients who have early deaths. They have spent 2 months in the hospital and you’ve spent so much time with their families and gotten to know them. They stick with you.

Similarly, when you’re taking care of a patient with chronic graft-vs-host disease and every therapy you throw at them can’t halt the progression, or they’ve gotten to a level of morbidity where you know they’re suffering on a daily basis, that’s tough. It’s tough to watch that. It’s tough to take solace in that you may have cured their malignancy but you have traded it for another disease that really affects their quality of life. All these areas are important. We all accept that. We’re encouraged by the progress over the last few years, and we look forward to the next few years with the research that’s going on and what we’ll partake of.

Thanks to all of you on the panel for this rich and informative discussion, and thank you to our viewing audience. We hope you found this OncLive® Peer Exchange® discussion to be useful and informative.

Transcript Edited for Clarity