Attacking Acute Graft-Versus-Host Disease From Multiple Angles

Acute graft-versus-host disease (aGVHD) is the most frequently encountered, life-threatening complication following an allogeneic hematopoietic stem cell transplant (aHSCT). In a live virtual symposium at the 2021 ASHP Midyear Clinical Meeting, 3 experts shed light on the role of the pharmacist in identification, prevention, and treatment of this deadly complication in a presentation titled Acute Graft-Versus-Host Disease Prevention and Treatment: Defining the Role of the Health-System Pharmacist.

In the beginning of the presentation, Andrew Lin, PharmD, BCOP, emphasized that GVHD remains a major cause of morbidity and mortality following aHSCT and noted 30% to 70% of aHSCT recipients develop aGVHD. He explained the pathophysiology and risk factors for development of aGVHD before reviewing diagnosis and staging criteria. The incorporation of biomarkers into risk assessment, highlighted Dr Lin, is a way to improve outcomes prediction for patients with aGVHD. Dr Lin noted that while there are no FDA-approved agents for prevention of GVHD, the most frequently used regimens include cyclosporine, tacrolimus, mycophenolate mofetil, cyclophosphamide, and methotrexate; tacrolimus plus methotrexate is considered the standard of care for patients with matched, related and matched, and unrelated donor aHSCT.

Nicole Watts, PharmD, BCOP, shifted the focus to management of aGVHD, explaining the first-line treatment is topical steroids for grade I aGVHD and systemic steroids are used for grade II-IV aGVHD. Management of aGVHD is complex, explained Dr Watts, because of heterogeneity of patient clinical presentation and lack of randomized controlled trials to guide treatment selection. Options for management of steroid-refractory aGVHD in the National Comprehensive Cancer Network guidelines include the following:

Ruxolitinib is the only therapy approved by the FDA for treatment of steroid-refractory aGVHD. Dr Watts presented data illustrating improvement in best overall response, ability to discontinue steroids, and improvement in overall survival with ruxolitinib compared with physician’s choice of therapy. Adverse effects frequently observed with ruxolitinib included thrombocytopenia, anemia, and cytomegalovirus infection. Other therapies highlighted by Dr Watts included AAT and tocilizumab, and several pipeline therapies.

In the final third of the presentation, Zahra Mahmoudjafari, PharmD, BCOP, DPLA, focused on the role of the clinical pharmacist in the care of HSCT recipients, noting the role has been endorsed by the American Society for Transplantation and Cellular Therapy, National Marrow Donor Program, Hematology/ Oncology Pharmacy Association, and the American College of Clinical Pharmacy. In this role delineation, Dr Mahmoudjafari highlighted pharmacists as experts in:

• Medication management

• Patient care

• Planning for transitions of care

• Education

• Research

• Quality improvement

Zahra Mahmoudjafari, PharmD, BCOP, DPLA, emphasized that “studies have demonstrated the value of clinical pharmacists in the setting of HSCT due to medication review, management and education, and significant time savings for providers through facilitation of insurance authorization, medication coverage appeals, and access to co-pay assistance programs, in addition to chemotherapy order preparation, immunizations, and pillbox fill.”