Guiding Principles in the Management of cGVHD

Pharmacy Times interviewed Clinical Forum moderator Gabriel Hinojosa, PharmD, BCOP, clinical pharmacy specialist, division of hematology and oncology, UT Southwestern Medical Center, on the role of the oncology pharmacist in the management of chronic graft versus host disease (cGVHD). Hinojosa also discusses how the pharmacist collaborates with other members of the patient care team, guiding principles when deciding how to treat patients, and significant data that have impacted clinical practice.

Pharmacy Times: What is the role of the oncology pharmacist in the management of chronic graft versus host disease (cGVHD)?

Gabriel Hinojosa: So, the role of the transplant, or oncology pharmacist, in the management of patients with cGVHD really is very complex. cGVHD may impact nearly every organ system of the body and it affects every patient a little bit differently, so really, no 2 patients will be the same and the pharmacist really plays a crucial role both in the initial treatment selection and tailoring that to that specific patient, as well as all the additional supportive care aspects that come along with that. For cGVHD, we often use many topical therapies for more mild cases—including skin creams, eye drops, mouth rinses, inhaled medications, just to name a few—and so, the pharmacist can help select the most effective treatment agent in each of those categories for the patient depending on what type of symptoms or organ involvement that they have. We also play a large role in helping with the initial dosing of systemic steroids. And then, of course, assessing if and when a patient needs to be transitioned to a different systemic therapy either to minimize steroid use or maybe a patient who has not responded adequately to steroids. But I will say, 1 of the largest roles that the transplant pharmacist plays in all this, is ensuring that we provide the appropriate supportive care to these patients.

So, a few examples…all patients with cGVHD have been described to be functionally asplenic, and these patients would require prophylaxis coverage for encapsulated bacteria with drugs like penicillin VK. Patients on systemic steroids should also be taking proton pump inhibitors for stress ulcer prophylaxis, and patients on high-dose steroids or other immunosuppressive agents will often require antifungal medications to protect them from invasive mold infections. So, the largest part of the transplant pharmacist in all of this is making sure that none of these complexities of the supportive care regimens fall through the cracks.

Pharmacy Times: How does the oncology pharmacist work with other members of the patient care team when making treatment decisions around cGVHD?

Hinojosa: The transplant oncology pharmacist works very closely with a multidisciplinary team of nurses, physicians, and other advanced practice providers to assess the patient's overall state and determine the best course of action. This team does most of the information gathering, the pharmacist often is not very involved in the information gathering side, but once we have all of the details, the pharmacist plays a very crucial role with this team in determining the most appropriate therapy and how to drive our therapy choices based on which organ sites are involved with cGVHD.

Pharmacy Times: What are the guiding principles in the treatment of cGVHD for oncology pharmacists?

Hinojosa: Guiding principles for the treatment of cGVHD may vary significantly based on the organ site involvement and severity, but I would say the large overarching goal for the pharmacist is to achieve a response using the lowest dose and shortest course of steroids necessary. Of course, steroids are not benign therapies at all, and long-term use of these agents are certainly associated with a long list of potential toxicities. Due to the high response rate and fast time to response, steroids remain our first-line therapy, but we're continually searching for strategies to minimize the amount of time that patients require steroids, and 1 of the largest guiding principles for the pharmacist is to make sure that we are managing those steroids appropriately.

Pharmacy Times: Are there data in the treatment of cGVHD that have impacted clinical practice recently?

Hinojosa: The most compelling data within the last few years for the management of cGVHD specifically came from the ROCKstar study that brought belumosudil (Rezurock; Kadmon Pharmaceuticals) to the market. ROCKstar evaluated belumosudil for the treatment of steroid refractory cGVHD after 2 or more lines of prior therapy. The study compared the novel agent belumosudil against best available therapy, and this included a very realistic patient population of heavily pre-treated patients, many of whom had failed previously other FDA-approved therapies for cGVHD, such as ibrutinib (Imbruvica; Janssen Biotech, Pharmacyclics) or ruxolitinib (Jakafi; Incyte Corp). So, this trial really did a good job at mimicking the patient population that we would see in clinical practice.

Belumosudil in the ROCKstar study did demonstrate efficacy in all organ sites. The primary endpoint was overall response rate, and this was achieved in 75% of patients, which was similar to overall response rates that we had seen in the REACH3 trial that brought ruxolitinib to the market. Maybe the most exciting part of all of this was the novel mechanism of action that provided anti-fibrotic properties. This makes belumosudil especially helpful when treating patients with fibrotic lung cGVHD or patients with fibrotic skin changes.

Pharmacy Times: Currently, what are you keeping an eye on in the field of cGVHD treatment?

Hinojosa: There are currently several drugs in the pipeline that seem very promising for the treatment of cGVHD,particularly there are several myelofibrosis drugs currently being studied that seem very promising in late phase data, and I'm really excited and hope to see data coming out on some of these agents early in 2024.