Post-Conference Perspectives: Advances in Chronic and Acute Graft-versus-Host Disease - Episode 7
Joseph H. Antin, MD: What we’re looking for are supplementary drugs that control the inflammation of GvHD [graft-versus-host disease] but do not inhibit the immune system. And ruxolitinib fits into that category. This is a way of adding a drug to our baseline framework of corticosteroid therapy that can reduce the inflammatory components, reduce the abnormal cytokine production, and contribute to a remission induction without fully compromising the immune system.
Without any definitive clinical trials being available, a number of years ago many transplant clinicians started to use ruxolitinib because of its beneficial effects in preclinical data in mice. And I think this was in significant degree amplified by a paper by Robert Zeiser, MD, that was in Blood several years ago, which was not a clinical trial, it was an accumulation of European experience in the use of ruxolitinib in patients with steroid-resistant both acute and chronic graft-versus-host disease.
And albeit an experiential analysis as opposed to a clinical trial, it was convincing that the drug was useful, and I think many of us off-label began using it on a routine basis in our patients. And so the various REACH trials I think will be very well received because we will now be able to put a solid research framework behind what we believe clinically has been an effective drug.
The REACH3 trial, which is a randomized trial of ruxolitinib plus corticosteroids versus best available therapy, will be extremely important in providing an experimental basis for what I think many of us have been doing clinically for a long time, which is using ruxolitinib in management of patients who have not responded well to steroids in graft-versus-host disease.
What is actually more interesting is whether drugs such as ruxolitinib will be useful as part of primary therapy. Waiting until a patient becomes steroid resistant of course is not the most desirable strategy because there will be some manifestations of GvHD that are irreversible. And if the drug can be given safely in combination with steroids without increasing the risk of infection, and by ameliorating any degree of steroid toxicity and yet controlling the graft-versus-host disease, I think that’s really the more desirable approach than a trial in patients who are already steroid resistant.
Transcript Edited for Clarity