The Future of Treating GVHD

Transcript:

Yi-Bin A. Chen, MD: Keeping with the emerging trend of moving away from broad systemic immunosuppression for graft-versus-host disease, there have been a few other agents that have been used. And all of these agents target specific pathways in hopes of trying to prevent or treat graft-versus-host disease. The proteasome inhibitors, such as bortezomib, had shown promise in single-center studies for graft-versus-host disease prevention. But when taken to larger studies, they were no different than our standard.

…At Mass [Massachusetts] General Hospital, we have done a lot of work with the monoclonal antibody vedolizumab, which to prove for the treatment of inflammatory bowel disease. Vedolizumab modulates lymphocyte trafficking to the intestines and has been shown to have some success in the treatment of steroid refractory intestinal graft-versus-host disease. And we’ve now moved to larger trials in prevention, including an ongoing phase III trial.

α-1 antitrypsin is another agent that has shown success in the treatment of steroid-refractory graft-versus-host disease. It is now being taken at larger trials, not only in prevention but also in up-front treatment. For chronic graft-versus-host disease, we look forward to the follow-up of results from the trial studying KD025 as a ROCK (Rho kinase)…inhibitor made by Kadmon Holdings, Inc, whose results from phase III studies are quite compelling, and we look forward to seeing the long-term results and, possibly, approval for this drug to treat our patients with chronic graft-versus-host disease.

The prevention and treatment of acute and chronic graft-versus-host disease remains an unmet need. While we have a lot of excitement from all of the agents that we’ve discussed and the ongoing trials, we have not reached success as of yet.

Specifically, certain subsets remain very difficult to treat. This includes patients with steroid-refractory acute intestinal graft-versus-host disease, where we may have to rethink our paradigm of how we treat. For graft-versus-host disease, this includes patients with scleroderma and also those with bronchiolitis obliterans syndrome.

The development of organ-specific treatments may be what we have to move to instead of thinking about graft-versus-host disease as 1 disease. Combining these organ-specific treatments with systemic therapies may be how we get ultimately to success.

Lastly, rethinking how we conduct clinical trials in this population is of utmost importance. The heterogeneity of our patients that have been included in prior trials has likely contributed to our lack of success. Better ways to risk stratify patients either clinically or by the use of biomarkers will be paramount to how we conduct trials in acute graft-versus-host disease. Developing better end points that are potentially based on nonclinical observations such as biomarkers or other methods will be an advance in this field. Chronic graft-versus-host disease is far more heterogeneous than acute. And developing a way to risk stratify those patients, but more importantly, ways to actually assess accurate response is of upmost importance as we move forward.

Transcript Edited for Clarity