Inside the Clinic: Acute Graft-versus-Host Disease - Episode 7

Ruxolitinib for Steroid-Refractory Acute GVHD


Yi-Bin A. Chen, MD: As I’ve mentioned, a really exciting development for our field was the first approval, or the approval of the first agent we have for graft-versus-host disease [GVHD]. That was for ruxolitinib [Jakafi], and that was approved in May of 2019 for the treatment of steroid-refractory acute graft-versus-host disease. Zack, can you discuss what the mechanism behind using ruxolitinib for graft-versus-host disease is?

Zachariah M. DeFilipp, MD: Sure, Yi-Bin. Ruxolitinib is a small molecule inhibitor of Janus kinases 1 and 2, or JAK1/2. Ruxolitinib previously received FDA approval for the treatment of patients with myelofibrosis as well as patients with a condition called polycythemia vera. However, what we’ve learned is that the JAK signaling pathway is also very prominent in patients who have acute graft-versus-host disease. There are a number of important cytokines that signal through the JAK signaling pathway, and these cytokines also influence a number of important immune regulatory cells that can further worsen the pathophysiology of acute graft-versus-host disease.

Ruxolitinib was recently FDA approved for the treatment of steroid-refractory acute graft-versus-host disease in adult patients as well as in pediatric patients age 12 years or older. This approval came largely based on the results of the REACH1 trial. This was a multicenter, open-label study to treat patients who had steroid-refractory acute graft-versus-host disease with ruxolitinib in combination with systemic corticosteroids.

In this study, there were multiple categories of patients who were deemed to have steroid-refractory disease. These categories were alluded to earlier by Yi-Bin. One category included patients who had worsening of their graft-versus-host disease within 3 days of steroid therapy. Another category included patients who had persistent graft-versus-host disease symptoms despite at least 1 week of therapy. And then there were additional patients who either flared during their steroid taper, or, for other reasons, were not able to tolerate the steroid taper.

In this study, 71 patients with steroid-refractory acute graft-versus-host disease were treated. The primary endpoint of the study was to evaluate the overall response rate at day 28, which was an evaluation of the percentage of patients who had either a complete response, a very good partial response, or a partial response of their graft-versus-host disease after 4 weeks of treatment, and to also evaluate the median duration of response.

In the study, 55% of patients achieved an overall response by day 28 [the primary endpoint]. But with further follow up, the best overall response rate of what percentage of patients had a response at any time in the study was 73%. Responses were seen across all of the categories of steroid-refractory patients. Responses were also seen in all organs that were involved in the GVHD—both the lower and upper GI [gastrointestinal] system, the skin, and the liver. At the most recent evaluation of follow up, the median duration of response is at 11 months, and that will be updated with further updates of the clinical dataset. At day 28, more than 50% of patients were able to decrease their steroid dose by at least 50%, which is a huge factor in understanding the toxicities related to GVHD treatment.

Transcript Edited for Clarity