Single Pediatric Transplant Center Experience with Belumosudil As a Potential Treatment for Chronic Graft Vs Host Disease in Adolescents and Young Adults

Background Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic cell transplant, causing significant morbidity and late non-relapse mortality in the post-transplant population. Approximately 5,000 people in the United States develop cGVHD each year. Standard treatment consists of high dose steroids; however, steroids only work in about half of patients and long-term use is limited by their toxic side effect profile. Belumosudil is an oral selective inhibitor of Rho-associated coiled-coil–containing protein kinase 2 (ROCK2) currently FDA approved for treatment of adult and pediatric patients 12 years and older with cGVHD after failure of at least two prior lines of systemic therapy. Belumosudil works by reducing type 17 and follicular T helper cells via downregulation of STAT3 and enhancing regulatory T cells via upregulation of STAT5. Current data suggests belumosudil may effectively treat patients with steroid refractory cGVHD; however, safety, efficacy, and dosing data are limited in the pediatric population. Methods We did a retrospective review of all the patients undergoing cGVHD treatment at Children's Hospital of Orange County. Of those we identified 8 cases treated with Belumosudil since September 2021 to September 2023. For safety profile we reviewed levels of serum creatinine, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP). We also graded the severity of their cGVHD and its progression or resolution. We also collected all the other drugs that the patients were and reviewed signs of potential drug interactions. Results Patients’ demographics included age range from 12 to 20 yrs; 4 Male and 4 Female. All 8 patients had severe cGVHD at max grading. 7 had skin involvement. 6 had lung involvement. 1 with eye; 1 with liver; 1 with Mouth and 1 with GI involvement as well. All 8 patients tolerated the Belumosudil well based on their liver enzymes and renal function without any major drug interactions. 4 patients already had their liver enzymes elevated at the time of starting treatment but then subsequently showed improvement after starting Belumosudil. Except the last patient who was recently started all patients showed significant improvement in their cGVHD symptoms. One patient was successfully weaned off and Belumosudil was stopped after resolution of cGVHD. Another patient is weaned as cGVHD symptoms continue to improve. Conclusion Here we describe one of the largest collection of adolescent and young adults treated at a pediatric transplant center showing that Belumosudil is potentially an effective and safe treatment for adolescents and young adults with cGVHD including those with liver involvement and those on other drugs for anti-fungal and relapse prophylaxis. Further pediatric studies are required to establish long term safety and efficacy including potential biomarker studies.