Frontline Treatment Options for Chronic GVHD

Transcript:

Yi-Bin Chen, MD: Many of the patients I see in my clinic are afflicted with chronic graft-vs-host disease, and it’s the most important determinant of long-term quality of life. When we talk about chronic graft-vs-host disease in studies and in these discussions, we’re generally referring to patients who require systemic therapy. But there are many patients we see before they reach that point for whom we try local therapy first. The most common organs involved in chronic graft-vs-host disease are the eyes, mouth, and skin. If the disease is not as severe, or if it’s limited to 1 or 2 of those organs, we’ll often try local and topical therapies in efforts to avoid the toxicities of the available systemic therapies for our patients. Many of these patients have been on steroids before or have gone through a lot in their treatment. Adding on systemic therapies has risks, and they’re not trivial.

For dry eye syndrome or a feeling of sand or irritation in the eyes, eye drops are the best way to focus therapy. We collaborate with ophthalmologists, who see most of our patients, starting around 6 months after transplant. We work with them for patients who require therapy. The eyedrops we prescribe include steroids…artificial tears for support and lubrication. We’ve used Restasis [cyclosporine], autologous serum tier, and Xiidra [lifitegrast], which is a target against another lymphocyte-trafficking molecule—all the way up in potency, depending on the patient’s severity. We also use specialized contact lenses, called scleral lenses, for patients who require that. There are physical procedures that can be performed in the eyes too, in terms of tear duct occlusion or punctal plugs, and this is at the discretion of our collaborating ophthalmologist.

For the mouth, we have a collaborating oral medicine physician, and we use various amounts of oral rinses that help with relief. These include dexamethasone, clobetasol, and tacrolimus rinses. We use steroid paste and target focal ulcers, and our collaborating oral medicine physician often performs injections localized for problematic spots. For the skin, it depends on how much of your body surface area is involved; you can put only so much cream, lotion, or ointment on. Most of these lotions and creams are corticosteroid based. We have a topical tacrolimus formulation that’s approved for pediatric eczema, and if we’re able to get access, we can use that as well. In general, we need more local therapies. Taking the novel agents that we will talk about in this discussion and seeing if we can obtain localized formulations would be a huge advance.

For patients who require systemic therapy for chronic graft-vs-host disease, unfortunately, we still use systemic corticosteroids, which has been the backbone for the last few decades. Hopefully, we’ll make improvements on that very soon. Most of these patients are outpatients, so there are oral formulations that we use, the most common being prednisone. The dose we use is somewhere between 0.5 to 1 mg/kg per day for a patient. We dose it between ideal and actual body weight, obviously with corrections for the extremes. In our practice, we tend to lean more toward the 0.5 mg/kg per day. The reason being, we don’t think steroids are the best treatment, but they’re the standard. Steroids have well-known toxicities: steroid-induced diabetes, psychosis, osteoporosis, hypertension, predilection for infection. Limiting the exposure to systemic steroids is a huge motivation for us, but we often need the steroids to treat graft-vs-host disease. If the clinical manifestations of the chronic graft-vs-host disease looks inflammatory, with active inflammation, then we’ll lean toward the 1 mg/kg dose. But in general, we’re right around the 0.5 mg/kg per day.

One big motivation in the field of chronic graft-vs-host disease is to add additional agents onto steroids to reduce the systemic exposure to steroids? Or can we substitute steroids for specific patients with chronic graft-vs-host disease? For the typical patient, I use steroids alone because that’s the standard of care, but there are certain patient clinical subtypes that we all dread adding steroids to. These are patients we know will suffer significant toxicity to steroids. They have brittle diabetes or severe osteoporosis or have had significant opportunistic infections, and we know that adding systemic steroids at that point for the treatment of chronic graft-vs-host disease will lead to a high risk of morbidity and even mortality in certain cases.

For certain patients, can I add something else for first-line therapy to taper the steroids faster? For some, I’ve used ruxolitinib with or without steroids in the first line. In the past when, we didn’t have access to the agents we do now, we’ve used first-line ECP [extracorporeal photopheresis], or photopheresis. Many centers will increase the calcium inhibitor, or whatever medications patients were on for prophylaxis to begin with, or perhaps were on a taper. We generally don’t do that in our practice, but I understand why certain providers would do that. I’ve also added rituximab as well as in the first line. This is all [because] we don’t think the steroids will work for that patient’s manifestations, or because we fear the complications the steroids will cause.

Transcript edited for clarity.