Treatment Approaches for Patients With Graft-Vs-Host Disease May Require Flexibility

In Pharmacy Times Clinical Forum discussions on the clinical management of chronic graft-vs-host disease (cGVHD), moderators noted that based on data from 2013 to 2018, approximately 42% of patients who underwent allogeneic transplants were diagnosed with cGVHD within 3 years. Of those patients, 71% required 2 or more lines of therapy to treat the disease. They also explained that the condition is the leading cause of non–treatment-related mortality in patients, with cumulative incidents by 5 years at approximately 22%, and of these, 38% are because of GVHD. Moderator Gianni Scappaticci, PharmD, a clinical pharmacy specialist in bone marrow transplant and cellular therapies at Michigan Medicine in Northville, Michigan, said that providers “cannot completely get rid of [GVHD],” so being able to better predict—or possibly prevent—and treat transplant-related complications can be significant when offsetting the development of GVHD. Additionally, understanding the pharmacist’s role in this treatment space can be significant for pharmacists when fully optimizing individualized care for patients.

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According to moderator Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA, a clinical pharmacy manager in the Division of Hematologic Malignancies and Cellular Therapies at the University of Kansas Health System in Kansas City, there are currently 3 FDA-approved agents for the treatment of patients with GVHD: ibrutinib (Imbruvica; Janssen Biotech, Inc, and Pharmacyclics LLC), which was approved in 2017; belumosudil (Rezurock; Kadmon Pharmaceuticals, LLC), which was approved in July 2021; and ruxolitinib (Jakafi; Incyte Corporation), which was approved in September 2021 and has indications for cGVHD. Ruxolitinib and ibrutinib may be used following 1 line of therapy, but belumosudil is indicated after 2 or more lines of therapy. Mahmoudjafari also explained that as far as treatment goes, it is generally “jury’s choice,” especially at her organization.

Mahmoudjafari noted that from her experience, treatment for GVHD consists of either belumosudil or ruxolitinib alone or a combination of the two, and in the pediatric setting, it is preferred that patients initiate treatment with belumosudil rather than ruxolitinib. Additionally, panelist Chelsea Minor, PharmD, BCOP, a clinical pharmacist at Washington University School of Medicine in St Louis, Missouri, explained that belumosudil has proven to be better tolerated in comparison with ruxolitinib in the real-world setting. She also noted that the treatment demonstrated positive responses and was well tolerated by patients in a prior small study. The moderators also warned of the adverse effects (AEs) or complications that can arise when using steroids, particularly long term, and that within 2 years of taking steroids, up to 50% of patients eventually become resistant or dependent.

“The prolonged steroid use [also] increases [risk of] infections—so viral, fungal—weight loss, bone loss, risk of myopathy, diabetes, hypertension, and cataract formation. This is not a comprehensive list, but steroids long term are not good for us, and so that’s the goal of adding or giving additional therapies,” explained Scappaticci.

One benefit of treating GVHD with belumosudil, explained moderators Mahmoudjafari and Mary McGann, PharmD, a pharmacy clinical specialist in bone marrow transplant and cell therapy at Medical University of South Carolina in Charleston, is its dual mechanism that simultaneously targets the proinflammatory and fibrosis pathways. Additionally, panelist Brandi Anders, PharmD, a clinical pharmacy specialist in stem cell transplant and cellular therapies at Atrium Health Wake Forest Baptist in Winston-Salem, North Carolina, explained that the inhibitor also has its advantages because it has a lower rate of cytopenias—whether alone or in combination with steroids or immunosuppressants—than other treatments.

In addition, the ROCKstar study (NCT03640481), which was mentioned by McGann, evaluated 2 doses of belumosudil daily compared with twice per day in patients with cGVHD who had received at least 2 prior lines of therapy. The findings demonstrated that patients had overall response rates of approximately 74%, regardless of the dosing frequency. Safety profiles also appeared similar to that of ruxolitinib. McGann also described single-center, real-world data that demonstrated similar outcomes to ROCKstar, with patients achieving response rates of approximately 70% and without significant safety concerns. She emphasized that regardless of the treatment being used for patients with GVHD, it remains important to pay attention to patients’ organ responses.

As far as the role of the pharmacist in the GVHD treatment landscape, moderators and panelists all agreed that it is vital that pharmacists help patients effectively manage and remain adherent to their treatment regimens. In addition, panelists emphasized that pharmacists are also responsible for the tapering of medications or treatments—which can be aided with resources such as tapering calendars—and should have frequent touch points to check in on patients. Minor expressed that she tries to manage steroid-related AEs, and panelist Rachel Langley, PharmD, BCPPS, a clinical pharmacist in the bone marrow transplant clinic at St Louis Children’s Hospital in Missouri, emphasized her perspective on her role as a pharmacist in improving patients’ quality of life.

“Not only are we treating the patient, [but] a lot of times we’re helping their parents…I have [a patient] right now who has way more complications post transplant than he ever had with sickle cell disease…but then in terms of managing the medications and stuff too, it’s also helping. These poor kids, they have to take these nasty medicines, and [pharmacists are often] helping the parents find ways to get the meds down in their kids and things like that,” Langley said.

“Finding schedules that are easy [is important] because telling a kid to take [these medications]—even kids who swallow tablets—[when] there’s sometimes [up to] 15 tablets, [is] a lot for a kid to swallow. So helping them come up with schedules and things like that [can be significant].”

Further, McGann also noted the importance of monitoring and limiting drug-drug interactions while advocating for patients. Panelist Jeffrey Baron, PharmD, BCOP, a clinical pharmacist at Roswell Park Comprehensive Cancer Center in Buffalo, New York, echoed this by stressing the necessity of educating patients, whether about therapies, AEs, or adherence. The panelists also underscored that being able to anticipate when patients with GVHD will need to move on to the next step of their treatment can help with seamless transitions.

“I think sometimes for certain patients there are just a lot of barriers where they feel helpless, hopeless…especially when they’re not coming from our pharmacy,” explained Breanna Taylor, PharmD, BCOP, a clinical specialist in hematology/transplantation and cellular therapies at Novant Health in Charlotte, North Carolina, in the discussion. “I feel like [transitioning from other centers makes] it all very difficult for the patient, and the confusion just causes them to almost give up. So I really just try to follow closely for certain patients, to make sure [they get] from beginning to end.”

Pharmacists must also remain flexible given the advancements in health care and be able to collaborate with other health care professionals. Mahmoudjafari explained that with ongoing oncologic developments, remaining open to change is essential for pharmacists to effectively and efficiently treat patients with GVHD.