in cGVHD

Pharms Provide Significant Support in cGVHD

By Myles Starr

Chronic graft-versus-host disease (cGVHD), a difficultto-manage potential complication of allogeneic stem cell transplantation, requires multidisciplinary management, with pharmacists playing a key role on the care team.

Specifically, pharmacists can advise surgeons and oncologists on the most appropriate cGVHD treatments, check for potential drug interactions and help patients with the often emotionally and financially challenging work of obtaining the new and expensive drugs for the condition, according to three experts who shared these strategies with Specialty Pharmacy Continuum.

Given the prevalence of cGVHD, these collaborative efforts are essential. A 2018 survey of 84 articles related to cGVHD found the incidence of the condition ranged from 14% to as high as 90% between one and five years into treatment (Value Health 2018;21[3]:S441-S442).

Generally, cGVHD occurs 100 days or more after a stem cell transplant (Blood 2017;129[1]:30-37), according to Mohammad Maher Abdul Hay, MD, a hematologist at NYU Langone Medical Center, in New York City. The condition “is characterized by fibrosis and inflammation in a variety of potential sites in the body, ranging from the eyes to tendons to the GI [gastrointestinal] tract.” Typical symptoms, Dr. Hay noted, include nausea and vomiting, loss of appetite, eye dryness, lichen planus in the oral cavity and fibrosis in the lungs causing decreased physical exertion tolerance in activities such as walking. “Chronic GVHD, in contrast to acute GVHD, rarely affects the liver and is not accompanied by high bilirubin levels,” he said.

The risk for cGVHD depends on the donor recipient match. Mismatch-related donations usually occur with a haplotype-related transplant. For any treatment team concerned about GVHD, the most important and opportune times to prevent a patient acquiring the condition are when matching the transplant and during perioperative management of the patient’s immunosuppression, Dr. Hay noted. Although physicians—not pharmacists—determine the matching of donor and recipient, pharmacists do have an important role at this juncture, because prevention of cGVHD also relies heavily on choice of medications, he said.

During those early stages, “the most important role of the pharmacist is in assisting in the achievement of [a] therapeutic level of immunosuppressants,” said Doris M. Ponce, MD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center, in New York City. Patients are started on immunosuppressants before stem cell graft infusion, “and we have learned that early levels of immunosuppression are very critical in prevention of severe GVHD,” she said. “Thus, we aim to achieve and keep a stable therapeutic level throughout the early post-HCT [hematopoietic cell transplant] period. Our pharmacist are responsible for monitoring and keeping an optimal level of the immunosuppressants. Pharmacists also offer support in how to adjust the dose of the other drugs that are frequently used concurrently in transplant.”

First-Line Treatment

, When cGVHD does develop, first-line medications include corticosteroids. Because some patients are steroid-refractory and other patients who are initially responsive to steroids eventually will need to stop them to avoid complications, a change to second-line therapies, including extracorporeal photopheresis, ibrutinib (Imbruvica, Janssen) and ruxolitinib (Jakafi, Incyte) sometimes is necessary, Dr. Hay noted.

“In the case of severe GVHD, in my experience, and also looking at the data, at least 30% of patients are going to need to use a second-line therapy, such as ibrutinib or ruxolitinib,” he said. “Of those, another 30% will need to go to [another alternative], such as belumosudil [Rezurock, Kadmon Pharmaceuticals]. Importantly, if there are interactions with other drugs, pharmacists will tell us. For example, with ibrutinib, they’ll note that the patient needs to have a certain number of platelets because there is a risk of bleeding.”

As for ruxolitinib, the drug can activate viruses, “so pharmacists will remind us that we need to follow up for possible cytomegalovirus infections with a patient,” Dr. Hay said.

Belumosudil, a kinase inhibitor approved by the FDA in July 16, 2021, represents “a breakthrough in treating cGVHD, partly because it has something different than anything we have seen in cGVHD—it actually can destroy fibrosis, while the others can only block inflammation; they don’t reverse fibrosis,” he stressed. “For example, some cGVHD patients present with tendon issues, so they cannot flex their arms because of fibrosis. This can be reversible with belumosudil. The same is true for lung inflammation. That medication in particular has an advantage over the others used to treat cGVHD, but it is only approved as a second- or third-line treatment.” (The prescribing information for belumosudil states that the drug is “indicated for the treatment of adult and pediatric patients 12 years and older with … chronic GVHD after failure of at least two prior lines of systemic therapy.”)

Assistance With Insurance

The pharmacists’ role in treating cGVHD is not limited to clinical recommendations and monitoring. As noted, they can be important conduits of information between doctors, patients and

insurance companies. “Patients will view the relationship with their pharmacist differently from the relationship with their oncologist,” said Nancy M. Nix, PharmD, a pharmacy oncology clinical coordinator at Ballad Health, in Johnson City, Tenn. “They will tell you things about their medication that they won’t tell the doctor because they think doctors [focus primarily on] their physical care, and so they choose to tell the pharmacist about their drug care. But the physician really needs to know all this information before he or she makes a choice of treatment, and due to our role, we can relate this information to physicians.”

Dr. Ponce agreed that pharmacists can play a critical role in helping patients and providers navigate payment issues, including appealing denials of initial request for coverage. Especially for uninsured patients, pharmacists also are indispensable in enrolling patients in drug company discount programs, Dr. Ponce noted. “Many insurance companies ask for additional information, which our pharmacies will provide,” she said. “Many of these medicines come from a specialty pharmacy. There are very specific rules about how to get the drug, and our pharmacy continuously adapts and improves as far as getting access to the medication. So, pharmacists’ involvement in managing cGVHD is really essential from many different perspectives.”

The coverage issues are not just anecdotal. In a 2018 multicenter survey, 34% of patients experienced delayed or denied insurance coverage for cGVHD treatments (Biol Blood Marrow Transplant 2019;25[3]:599-605). One frequent reason for denied claims involves sequence of therapy, Dr. Nix noted. “Many payors have therapy pathways built into their formulary that require a patient try and fail a therapy based on the consensus guidelines,” she said. “Pharmacists can

support their patients by providing clear information to the prescriber concerning what therapy must have been tried and failed prior to approval of a subsequent therapy.”

In taking such actions, pharmacists act as an important node between the prescriber, insurance companies and patients, Dr. Nix noted. But it is their clinical role that arguable can have the largest impact. “Prescribers have embraced the role of the pharmacist in being able to aid them in choosing, not just the most effective cGVHD and other treatments, but avoiding potential complications as much as possible,” she said. “Physicians who train at centers that have an integrated pharmacy will absolutely pick up the phone and say, ‘I’m not sure about the drugs they are taking. Can you look at the interactions?’ Doctors definitely view us as a resource to aid in the care of the patients and make it more streamlined overall.”

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Allogeneic transplants contain large amounts of donor immune cells that can trigger a reaction against the recipients’ cells and result in graft-versus-host disease.

Source: Crown Bioscience.

Drs. Abdul Hay and Nix reported no relevant financial disclosures. Dr. Ponce reported financial relationships with CareDx, Ceramedix, Evive Biotechnology (Shanghai) Ltd., Incyte and Kadmon Corporation.