Expert Discusses Advances, Unmet Needs in GVHD Treatment

While treatment for graft-versus-host disease (GVHD) has improved in recent years, thanks to drugs such as ruxolitinib (Jakafi), there are still unmet needs for patients who experience this toxicity, especially for those who are steroid refractory, explained Madan Jagasia, MBBS, MMHC.

Jagasia, chief medical officer at Vanderbilt-Ingram Cancer Center, recently sat down with OncLive, a sister publication of Oncology Nursing News, to discuss GVHD and how to best manage the disease.

Oncology Nursing News: Can you give a broad overview of GVHD?

Jagasia: Graft-versus-host disease is an immune complication for allogenic stem cell transplant affected by dormant T cells and probably dormant B cells as well. We currently divide GVHD into 2 groups: acute GVHD, which we tend to see early on after transplant and chronic GVHD, which typically starts around 2 to 3 months post-transplant and really has a heterogenous manifestation.

If you look at it from a patient's lens, post-transplant there are 2 major limitations of a successful transplant. One is GVHD and the other is relapse of the underlying disease. As we improve the outcomes of GVHD, whether it's prevention, treatment of acute GVHD or treatment of chronic GVHD, we should be overall improving the outcomes of transplant patients.

What are the treatment options for GVHD?

Treatment options for GVHD should be divided into 2 groups: [those for] acute GVHD, and [those for] chronic GVHD.

In acute GVHD, the frontline therapy is still based on corticosteroids. The field that is changing over there is can we get more accurate data based on biomarkers, as to which patient is going to be more trouble? Identify that subset of patients and augment therapy to adding other agents in addition to corticosteroids. On the other hand, we need to think about as patients with acute GVHD with super low risk of getting [GVHD] and ask the question and de-escalate therapy so that you don't expose them to the adverse effects of corticosteroids.

If a patient fails corticosteroids, we call that steroid-refractory acute GVHD, in that space today we have ruxolitinib that is FDA approved. So, the unmet need today is really 2-fold. Can we de-escalate therapy in patients who are not going to get into trouble? And what do we do when a patient has steroid-refractory acute GVHD that has failed ruxolitinib? That's still a big group of patients for which we do not have any wider options.

Moving on to chronic GVHD, frontline therapy is calcineurim inhibitors and corticosteroids. There we know corticosteroids do work, but when you look at that patient 1 year down the road, many of those patients are still on some corticosteroids and have moved on to subsequent lines of therapy. So frontline therapy of moderate to severe GVHD is an unmet need.

In terms of advanced chronic GVHD, ibrutinib is FDA approved. KD025 is looking really promising…There are other advances that are emerging in this field.

Can you discuss the toxicities of using ruxolitinib to treat chronic GVHD?

Ruxolitinib is a JAK1/JAK2 inhibitor that is very effective in acute GVHD, but it comes with a price. You're suppressing the immune system and the worry is that the suppression of the immune system will expose the patient to more infections.

Data will be coming out in the fall from a manuscript where we try to address this in a more granular manner. What it appears is that when ruxolitinib works, and the patient responds from a GVHD standpoint, the risk of infection actually decreases. It is the non-responders for ruxolitinib that are really giving the signal of the high infection rate. Thus, ruxolitinib non-responders is really the group that we need the scientific focus on to see how we can improve the outcomes of these patients.

A thing to keep in mind is that ruxolitinib is for patients who are steroid refractory...So as soon as a patient is refractory, stop the next line of therapy in the form of ruxolitinib. Don't wait too long. Don't expose the patient to unnecessary steroids, because unnecessary steroids generate the milieu of ongoing infections as well.