Frontline Treatment Options for Acute Graft-Versus-Host Disease

Shernan Holtan, MD, University of Minnesota, Minneapolis, Minnesota explores advances and unmet needs in the frontline treatment of patients with acute graft-versus-host-disease.

Transcript:

I'm Shernan Holtan, associate professor of medicine at the University of Minnesota. My focus is on graft-versus-host disease research. Let's talk about the frontline treatment of acute graft versus host disease. An unmet need in our field is significant reduction, or ideally, elimination of corticosteroids. There are so many side effects, as we know, from high-dose prednisone, including metabolic problems, hyperglycemia, hyperlipidemia, insomnia, effects on the bones and muscles, infection risk. And so, our field is working hard to see if we can find alternatives to prednisone.

We've had multiple studies recently that show that we likely can eliminate prednisone in the low-risk GVHD setting. The first study was conducted by the BMT CTN, called BMT CTN 1501, which randomized standard-risk acute graft-versus-host disease patients to sirolimus versus prednisone, and found essentially equivalent outcomes, with lower risk of complications including steroid myopathy with use of sirolimus. And so, this gives us 1 option to eliminate prednisone in patients with standard risk GVHD. There's also a recent publication in Blood, showing the use of itacitinib in the frontline standard risk setting. Another steroid-free option will hopefully be available outside of a clinical trial soon.

Now, the harder part is, what to do with patients who have high-risk acute graft-versus-host disease? These patients historically have had poor results with prednisone, with greater than 50% of patients needing second-line therapy, and a high risk of mortality related to graft-versus-host disease. The paradigm has been using high-dose prednisone, plus adding something to it to see if we could improve on the outcomes.

We recently published a paper using human chorionic gonadotropin plus epidermal growth factor. This is a commercially available preparation that goes under the trade name Pregnyl, in addition to prednisone for those who have life-threatening, high risk acute graft-versus-host disease. And with that combination, we showed excellent response rates at day 28. That was encouraging, so much so, that we wanted to explore using this in the frontline setting to see if we could reduce prednisone burden.

Our current study that is now enrolling patients, is using that same platform of Pregnyl plus the FDA-approved drug for the second-line treatment of acute graft-versus-host disease, which is ruxolitinib, plus steroids. But the study is a phase 1 dose de-escalation of prednisone. We're using the combination of the human chorionic gonadotropin preparation plus ruxolitinib in the first-line setting, and seeing if we can use that in combination with dose-deescalated prednisone, to see how low can we get the prednisone dose, even in people who have life-threatening graft-versus-host disease. To see if we can eliminate the side effects of prednisone, and have better overall outcomes, even in the high-risk population.

Source:

Pidala J, Hamadani M, Dawson P, et al. Randomized multicenter trial of sirolimus vs prednisone as initial therapy for standard-risk acute GVHD: the BMT CTN 1501 trial. Blood. Published online January 9, 2020. doi:10.1182/blood.2019003125

Holtan SG, Hoeschen A, Cao Q, et al. Phase II, open-label clinical trial of urinary-derived human chorionic gonadotropin/epidermal growth factor for life-threatening acute graft-versus-host disease. Transplant and Cell Ther. Published online August, 2023.
doi: 10.1016/j.jtct.2023.05.021