GVHD Cannot Be Wholly Prevented, so Effective Treatments Are Needed, Says Dr. Daniel Wolff

Daniel Wolff, M.D., Ph.D.

Patients who receive a stem cell transplant are at risk of developing graft-versus-host disease (GVHD), in which the donor’s immune cells attack the recipient’s body and cell. In August, the FDA approved Niktimvo (axatilimab) to treat chronic GVHD in patients who have progressed on at least 2 prior systemic therapies.

GVHD can occur as both an acute and a chronic disease. In this interview, Daniel Wolff, M.D., Ph.D., professor at University Hospital Regensburg in Regensburg, Germany, an investigator on the AGAVE-201 trial, which was used to support the approval, discusses the differences between chronic and acute GVHD, as well as the current measures to prevent GVHD from occurring.

This transcript has been slightly edited for clarity.

Managed Healthcare Executive® (MHE): How do the symptoms and management of chronic GVHD differ from acute GVHD?

Wolff: That's a good question and when the pathophysiology differs, the treatment differs as well. It doesn't differ with first-line treatment. Steroids are the first-line treatment in acute and chronic GVHD. The dose is different. Acute GVHD is usually treated with higher doses of steroids compared to chronic GVHD, but on the other side chronic GVHD patients are exposed to steroids for a much longer time than in the acute setting. Second line is not totally different. Ruxolitinib is now approved in second line in acute and chronic GVHD. After that, the agents used differ and also the approach differs.

Acute GVHD is an acute disorder, which has to be controlled very soon because otherwise it's a deadly disease. But it usually resolves, or you die. Chronic GVHD is a chronic disease where you usually don't die, but you are troubled with significant symptom load over a long time with significant treatment side effects and impairment of organs by the disease. It fulfills classic criteria for chronic disorders, and the treatment applied in chronic GVHD is given for much longer time and the aim is to control the symptoms, to resolve the organ damage and to get the patients finally, functionally tolerant. But some of those patients require immunosuppression lifelong or at least five to eight years, and that makes — in terms of management — the difference.

I also want to emphasize that acute GVHD only affects skin, gut and liver. While chronic GVHD can affect almost every organ you can think of, including ocular surface, the oral mucosa, it can affect the genital mucosa and lungs. There's hardly any organ which can't be affected by chronic, which makes it challenging.

MHE: What are the current measures taken to prevent GVHD and how do well do they work?

Wolff: That a rapidly evolving field. The standard immune suppression being the standard for almost 30 years was calcineurin inhibitor combined with methotrexate or [mycophenolate mofetil]. This resulted in the combination with peripheral stem cells in a chronic GVHD rate about 50% up to 70%. Now, for the last 10 years, new options have been developed using [anti-thymocyte globulin] or posttransplant cyclophosphamide that have decreased the incidence. Actually, using this approach, the incidence is now around 30% to 35%. So, it became less an issue, but it's still an issue.

There are new developments, which for instance involve graft engineering. I just want to mention the Orca-T platform, which is currently evaluated in clinical trial, which results in a chronic GVHD rate at around 5% to 10%. That's the next step forward. There are approaches made which could use this kind of platform of graft engineer or combined immune suppression, which makes it much less an issue than in the past.

Having said that, the idea that chronic GVHD will simply vanish and not occur anymore would be nice, but it's not realistic. Thinking about the use, for instance of donor lymphocyte to treat relapse after transplant, which results in chronic GVHD and thinking of patients who still develop chronic GVHD despite those new applications.

In summary, the good news is that the incidence is decreasing, but with some sobering aspect in there that this disease will not vanish completely. We still need effective treatments for those who are affected by the disease.