JAK Inhibitors in Steroid-Refractory GVHD

Bart L. Scott, MD:What are the data that support the use of ruxolitinib for patients who have steroid-refractory acute graft-versus-host disease [GVHD]? There was a clinical trial known as REACH1 where patients with steroid-refractory GVHD were treated with ruxolitinib. The overall response rate at day 28 was 54.9%. This was felt to be significant. It was a phase II study, and it’s one of the few agents that has been approved in that setting for steroid-refractory acute graft-versus-host disease. You would generally start patients out on 5 mg twice a day dosing of the ruxolitinib. The major issue with the dosing is thrombocytopenia, so you do have to be concerned about potential risk of bleeding and lowering of the platelet count.

I have some notable responses in patients. I have 2 patients who had steroid-refractory gut GVHD that we treated with ruxolitinib who had complete responses. And then we were able to successfully wean off the steroid therapy. Typically, when you have a patient with steroid-refractory gut GVHD, that has a horrible prognosis.

How do I establish who is appropriate for ruxolitinib therapy? Its indication is for steroid-refractory GVHD, so of course, you would treat patients up front with steroid therapy. And if they have persistent symptoms after 5 to 7 days of steroid therapy, and usually at that point you’re talking about 2 mg/kg, then I would consider that treatment. As I mentioned, thrombocytopenia can be an issue. So, if the platelet count is less than 50,000, I’m a little bit less reluctant to treat patients with ruxolitinib in that setting. If they have major bleeding complications, I’m also a little bit less reluctant to treat patients with ruxolitinib in that setting.

Transcript edited for clarity.