Exploring the Implications of the ROCKstar Regimen in Chronic GVHD

Corey S. Cutler, MD, MPH, FRCPC medical director, Adult Stem Cell Transplantation Program; director of Clinical Research, Stem Cell Transplantation; director, Stem Cell Transplantation Survivorship Program; institute physician, Dana-Farber Cancer Institute; and associate professor of medicine, Harvard Medical School, discusses the trial of belumosudil (KD025) in patients with chronic graft-vs-host disease (GVHD).

The ROCKstar trial (NCT03640481) met its primary end point of overall response rate in the enrolled patients with chronic GVHD. Because this drug showed efficacy, Cutler believes it will be approved for patients in this setting after at least 2 prior lines of therapy. In the future, combination regimens including belumosudil may be a possibility.

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0:08 | The ROCKstar study [was used] to test the activity of belumosudil in chronic GVHD. Chronic GVHD is both an inflammatory as well as a fibrosing disorder. So it initiates with inflammation in target organs. and the final common pathway of chronic GVHD is sclerosis or fibrosis. Belumosudil is an inhibitor of ROCK2, which is important both to control inflammation at the level of the germinal center and, in addition, it is the final common pathway for collagen deposition and myofibroblast differentiation. So it, in theory, can hit chronic GVHD both at the inflammatory as well as the fibrotic stage.

0:56 | This was a randomized phase 2 trial testing 2 different doses of belumosudil in chronic GVHD. The 2 doses were 200 mg once daily and 200 mg twice daily. The patients we enrolled here were above the age of 12 and had received 2 to 5 lines of prior GVHD therapy and were therefore resistant or refractory or had progressed after their prior line of therapy. So this was a patient population that was extremely advanced. In fact, these patients had at least 25 to 30 months of chronic GVHD when they entered the trial.

1:38 | This is going to be a very important compound to add to the armamentarium of drugs that we have for treatment of chronic GVHD. It will likely be approved with a label that includes 2 prior lines of therapy, although it will remain to be seen how practitioners will use it and how they will sequence this agent in comparison to the other commonly used drugs in steroid-resistant chronic GVHD. But there's no doubt that this is going to be an important drug in the future. We're going to have to figure out how to use this drug in combination with others, where it makes the most sense to rationally combine it with other agents, and what other exploratory platforms we can use this drug in.

2:23 | This is really the first drug that has sclerosis as its codominant mechanism of action. So I think there's very real reason to think that this drug could be combined with the other commonly used agents like tacrolimus and sirolimus, but as well the other agents that are used regularly in chronic GVHD, such as a ibrutinib or ruxolitinib. We certainly have to learn how to combine these agents in terms of toxicities and interactions. But it wouldn't be unreasonable to think about concomitant therapy with either of those 2 novel agents.