Real-world effectiveness and safety of belumosudil in pediatric chronic graft-versus-host disease: A retrospective cohort study

Abstract Background: Chronic graft-versus-host disease (cGVHD) remains a leading cause of non-relapse mortality and morbidity in pediatric patients following allogeneic hematopoietic stem cell transplantation (HSCT). While corticosteroids with or without calcineurin inhibitors are the mainstay of first-line therapy, many children exhibit suboptimal responses or intolerable toxicity. Current second-line options are limited by varying efficacy and safety concerns. Belumosudil, a selective ROCK2 inhibitor targeting both inflammatory and fibrotic pathways of cGVHD, has demonstrated promising efficacy and safety profile in adult patients with an overall response rate (ORR) of 74–77% in the ROCKstar trial and 73.3% in Chinese populations. Although it has been approved as treatment for steroid refractory cGVHD patients aged ≥ 12 years old, evidence in pediatric setting remains scarce. This study aimed to describe the effectiveness and safety of belumosudil in real-world pediatric populations.Methods: This retrospective cohort study included pediatric patients with cGVHD who received belumosudil at Children's Hospital of Soochow University between March 2024 and January 2025. Inclusion criteria were: (1) age ≤18 years with prior allogeneic HSCT; (2) persistent cGVHD requiring systemic therapy after failing ≥1 prior line of treatment; (3) completion of ≥4 weeks of belumosudil therapy. Exclusion criteria were: (1) diagnosis of post-transplant lymphoproliferative disorders; (2) history of liver or lung transplantation for cGVHD following HSCT. Belumosudil dosing was adjusted according to age and body weight. For patients aged <12 years, the dose was 200 mg/day for those weighing ≥24 kg, 100 mg/day for 15–24 kg, and 50 mg/day for ≤15 kg. The primary outcome was ORR. Secondary outcomes included changes in Lee Symptom Scale scores, corticosteroid dose reduction, and safety. Results: The study included 30 pediatric patients with a median age of 10.5 years (range: 2-16), including 16 children (53.3%) aged <12 years and 56.7% males. Median weight was 31.25 kg (range: 14-55). According to 2014 NIH criteria, 66.7% had severe cGVHD and 30.0% had moderate cGVHD. Nearly half (46.7%) had ≥2 organs involved, with lungs (63.3%) and skin (36.7%) being most commonly affected.Prior to belumosudil, 80% received ≥2 systemic therapies, with median 13 months from cGVHD diagnosis to belumosudil initiation. Median treatment duration of belumosudil was 24.1 weeks. Most patients had concurrent medications, including corticosteroids (80%), tacrolimus (43.3%), and ruxolitinib (40%).Responses were reported in 22 patients (73.3%, 95% CI: 54.1%-87.7%), including 1 complete response and 21 partial responses. Subgroup analyses showed particularly high response rates in patients with non-severe cGVHD (80.0%), those with ≥2 involved organs (85.7%), those with a time from cGVHD diagnosis to belumosudil initiation of ≤12 months (78.9%), and those who had received ≤2 prior lines of therapy (83.3%). Patients aged <12 years also exhibited a high ORR of 75.0%. Organ-specific responses were first evident at 1-month follow-up for most affected sites (excluding liver), with substantial improvement by 3 months. Organ-specific ORR rates were: oral cavity (75%), skin (72.7%), joints/fascia (71.4%), lungs (68.4%), eyes (60%), and gastrointestinal tract (60%). Two patients with liver involvement did not achieve response.Symptom improvement, as measured by the Lee Symptom Scale, was observed in 18 patients (60%), with a median score reduction of 4.5 points. Six patients showed a reduction of >7 points. Among the 24 patients receiving concomitant corticosteroids, 18 (75%) had dose reduced, with a median corticosteroids dose reduction of 61.2%.Adverse reactions occurred in four patients (13.3%). One patient had grade 3 abnormal liver function, which resolved after treatment interruption and hepatoprotective therapy. The other adverse reactions were grade 2, including leg muscle pain, cramping, hypertension, multiple muscle pain, left hypochondriac pain, and loss of appetite. Two required dose reduction. Conclusions: Belumosudil showed favorable response and safety in pediatric cGVHD patients in the real-world practice, with clinically meaningful symptom improvement and corticosteroid-sparing effects. The treatment was also effective in children under 12 years of age. These real-world findings support the use of belumosudil as a valuable therapeutic option for pediatric cGVHD patients.