Inside the Clinic: Acute Graft-versus-Host Disease - Episode 10

Novel-Based Approaches and the Future of Acute GVHD


Yi-Bin A. Chen, MD: I think we should mention there are several other efforts going on studying novel agents for the treatment or prevention of graft-versus-host disease [GVHD]. These include other JAK inhibitors. Ruxolitinib inhibits both JAK1 and JAK2, and the inhibition of JAK2 is thought to be responsible for most of the cytopenias that are observed. The newer JAK inhibitors are a bit more JAK1-selective. We are hopeful that they maintain their graft-versus-host disease action, but that we don’t observe as many cytopenias as well. So these are actively being studied.

There is a protein called alpha-1 antitrypsin, which is an approved agent that’s been given for decades for a congenital deficiency of alpha-1 antitrypsin. That’s being studied for the treatment of graft-versus-host disease as well. The preliminary data from our colleagues in Seattle, Michigan, and Boston have been compelling, and it will be studied in a national trial, giving alpha-1 antitrypsin with steroids for the treatment of graft-versus-host disease.

Other agents include agents that have traditionally been studied for inflammatory bowel disease. At Massachusetts General Hospital, we have been interested in a monoclonal antibody called vedolizumab that’s being used for ulcerative colitis and Crohn disease. These are just a few of the other agents that are actively being studied. I think you’ve heard from us why trials may have been difficult to show progress. I think all of us here are really gratified at the level of investment that science but also industry is pouring into our patient population. Already, we made a big step forward with ruxolitinib, and I think we will make more steps forward in the years to come.

I think the questions we’re looking at right now are based on what has been mentioned already in our fruitful discussion. One has been what Zack discussed, in how we can risk stratify patients and treat them differently. Two has been figuring out how we can incorporate these novel agents with the standard of care. Can they replace the standard of care, or are we just adding on? Third is, you heard about the patient journey from Colleen, which is not only what the patients go through physically to get better, but the mental and emotional toll it takes on the patient and their family. How are we able to shorten that? Are there agents that work faster? Can we speed up the kinetics so we don’t have to deal with all of that morbidity? I think all of us know that diagnosing and managing graft-versus-host disease is a team sport, and we’re thrilled to have colleagues who we work with each and every day who care for our patients the utmost and have allowed us to continue to do what we do. Last, I’ll pose a question to both of my colleagues. What advice would you share with other centers about managing patients with acute graft-versus-host disease, Colleen?

Colleen M. Danielson, NP: I think what you mentioned, the multidisciplinary approach to care. Having cared for patients in both the inpatient and outpatient settings, it’s different. But each setting requires a multidisciplinary approach, and that really gives the best care to our patients.

Yi-Bin A. Chen, MD: Zack?

Zachariah M. DeFilipp, MD: I think that it’s important to continue to look for new developments for our patients. As we’ve discussed today, the FDA approval of ruxolitinib is a huge breakthrough for our field of bone marrow transplantation, and specifically our patients with graft-versus-host disease. But we also know that there are still patients who need additional therapies or other avenues to get their treatments. So while ruxolitinib is now available for our patients and we should be able to offer this great new breakthrough for them, we should also continue to academically strive in clinical trials, to risk stratify and find individualized treatments for our patients.

Yi-Bin A. Chen, MD: In closing, I’d like to thank my colleagues for joining me today on this OncLive Insights® Inside the Clinic program. I hope all of you who have been with us along the way have found this conversation to not only be productive but also entertaining. Thank you very much.

Transcript Edited for Clarity