Bonnie J. Dirr, APRN: Let’s take another look [at] CB’s journey for our audience. Unfortunately, CB experienced progression. He presented to the clinic with lower extremity fascia changes now extending to his lower extremities [and] his upper extremities with bound down tissue. His ocular symptoms [include] dry crusting mucosa secretions and photophobia in over a 12-week period, despite titration up on the ruxolitinib [Jakafi], and his tacrolimus [Prograf] dose was brought back to therapeutic. There was consideration of adding ECP [extracorporeal photopheresis] as another line of therapy. Further attempts were made to taper his steroids in the setting of a limited response, as Dr Gooptu had highlighted before. With no response of moving forward with tapering steroids in the setting of waiting for the insurance approval to start ECP, 4 doses of rituximab were attempted to be delivered without success. He did receive his consult at Massachusetts Eye and Ear with one of our colleagues, Dr L, who is an expert in ocular GVHD [graft-vs-host disease], who we collaborate with on a regular basis. There were punctal plugs placed with good fit. There was steroid gel added for nighttime QHS. Preservative-free prewetting drops were continued, but the cyclosporine drops were discontinued secondary to lack of response. The patient completed 12 full weeks, 2 cycles of ECP, along with participation on a clinical trial utilizing abatacept [Orencia], with limited clinical response. The main improvement was only his ocular symptoms, leaving CB with scleroderma changes for his upper and lower extremities, with very bound down tissue, very much limiting his range of motion. There was an attempt to continue to taper his oral steroids. At such time, belumosudil [Rezurock] had just been FDA approved in the management of chronic [GVHD]. Dr Gooptu, can you please discuss the available systemic therapy in supporting the evidence for the patients with steroid-refractory chronic [GVHD], such as this drug, as well as clinical trials in the efficacy? Perhaps you can highlight some of the therapies in your choices for CB and possibly expand a little more broadly for our audience.

Mahasweta Gooptu, MD:CB is actually a great case because he developed chronic GVHD in a time when ruxolitinib and belumosudil also was not approved, and they actually got approved while his disease was evolving, which is very lucky for us and for him. Prior to belumosudil and ruxolitinib, the therapies that were available for steroid-refractory chronic GVHD all had response rates of 30% or lower. It was very hit or miss, because you never knew who would respond to which therapy. We would try to tailor therapies based on clinical manifestations, but it wasn’t perfect. Ibrutinib [Imbruvica] had been approved based on a single-arm study, but we have not had as much success with it as you might have hoped. And recently, a randomized study has shown no improvement of ibrutinib over steroids. So, I have never used ibrutinib a whole lot in my own practice. We tried ECP, with some limited response. We tried rituximab and we tried abatacept—which now we have published experience in steroid-refractory GVHD…and the response rates are encouraging but in CB’s case, it was not all that helpful. He was not one of the responders. I do think he derived some benefit from ruxolitinib, which is an extremely effective drug in the steroid-refractory GVHD setting. This has been published in the New England Journal [of Medicine], and the overall response rates were in the 50% range, which was far higher than any other agent used previously. We ourselves have anecdotally had numerous successes in the clinic with ruxolitinib. So, that was tried for CB at a dose of 5 mg twice a day because he was also on an antifungal. As Dr Inyang will point out, there’s an interaction between ruxolitinib and you do have to be mindful of the dose and adjust as needed. He did derive some benefit from ruxolitinib. However, he eventually progressed again and we were thinking of clinical trials. In fact, I almost signed him up for a clinical trial with…and at that point, belumosudil also became available.

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