Case 3: Ruxolitinib for Steroid-Refractory Acute GVHD

Corey Cutler, MD, MPH, FRCPC: I think it is worth mentioning that ibrutinib is approved in this indication. It was the first and the only drug approved in chronic graft-versus-host disease [GVHD]. It was a small study. It was a 42-person study with a fairly narrow entry criteria, but there are updated results available from that trial that were published not long ago by Edmund Waller, MD, PhD, FACP, as the first author, and the response rate was nearly 70%. Again, these were probably patients without advanced, very burned-out chronic GVHD. That has to be said, but it's hard to argue with a response rate of 69%. Do either of you have any experience using ibrutinib in chronic GVHD?

Daniel Couriel, MD, MS: I do. I think that there is a difference in everyday or out-of-clinical-trial experience with what the clinical trial shows because I think that the general trend is to leave ibrutinib for way too late in the game, when patients are not responding to anything. I think that ibrutinib gets undeservedly criticized and not because of lack of efficacy, as it was shown in the clinical trial. Although it was small, it was a good clinical trial, but the fact that the patient has, as you said Corey, a burned-out chronic GVHD that is likely not to respond to anything.

I think that one good thing to look at and to follow from the ibrutinib study is that is the kind of selection that we should do in our clinical practice. We should not wait until we get to a situation in chronic GVHD where treatment doesn't do anything because all the manifestations are irreversible. We should give the patient the opportunity to use these treatments earlier. I think that's the kind of population that you had in the ibrutinib study, which is a good thing to get from the study.

Corey Cutler, MD, MPH, FRCPC: There also is experience with ruxolitinib, and Usama alluded before to retrospective studies that looked at the activity of ruxolitinib in acute GVHD, and those retrospective reports did suggest that it is active in chronic GVHD, and we are all eagerly awaiting the results of the REACH3 trial. We talked about REACH1 and REACH2, but REACH3 is a randomized trial looking at ruxolitinib in steroid-refractory chronic GVHD. There aren't any early top-line results available, so we don't need to dwell on that, but there are certainly a number of other clinical trial agents that are promising out there. We've been actively involved with KD025, or the ROCK2 inhibitor, which appears to be a promising agent. Again, this is a drug that is still in development.

Transcript edited for clarity.