Background: As for chronic graft-versus-host disease (cGVHD), treatment options beyond traditional strategies remain limited. Belumosudil was approved by the U.S. Food and Drug Administration (FDA) in 2021 for patients with cGVHD who have received at least two prior lines of systemic therapy. However, belumosudil has not been approved by Chinese health insurance bureau until January 2025. This study aims to report a retrospectively, real-world, single-center clinical experience with belumosudil since January 2025 in patients diagnosis with cGVHD for at least two years.

Methods: A total of 17 patients with cGVHD who received belumosudil were retrospectively analyzed at Shandong Provincial Hospital affiliated to Shandong First Medical University, between January 2025 and July 2025. Demographic data, prior treatment regimens for cGVHD, together with the clinical responses and adverse events (AEs) of belumosudil were collected from medical records. Study endpoints included overall response rate (ORR) at 3 and 6 months, time to response (TTR), the improvement in Lee Symptom Scale (LSS) scores, and safety outcomes.

Results: Among the 17 patients who underwent allo-HSCT, 52.9% (n = 9) were male, with a median age of 35 years (range, 11–63). A history of acute GVHD (aGVHD) was present in 70.6% (n = 12). The median number of organs affected by cGVHD was 3 (range, 1–8), with 29.4% (n = 5) exhibiting involvement of four or more organs. The most commonly affected sites were the skin (82.4%, n = 14), oral cavity (58.8%, n = 10), eyes (29.4%, n = 5), and lungs (29.4%, n = 5). Resistance to the most recent prior therapy (including glucocorticoid, calcineurin inhibitors, mycophenolate mofetil, ruxolitinib, mesenchymal stem cells, etc.) was observed in 82.4% (n = 14). The median number of previous treatment lines was 3 (range, 1–5), with 82.4% (n = 14) having received two or more lines of therapy, and 17.6% (n = 3) receiving belumosudil as first-line treatment. The median time from cGVHD diagnosis to initiation of belumosudil was 27months (range, 24–72). All patients received belumosudil at a daily dose of 200 mg; 47.1% (n = 8) received concurrent treatment with ruxolitinib, and 58.8% (n = 10) with corticosteroids. With a median follow-up of 5 months (range, 2–7), the ORR was 70.6%, including 11.8% complete response (CR) and 58.8% partial response (PR). The median TTR was 2 months (range, 1–8). All three patients who received belumosudil as first-line treatment achieved PR. In patients who had received two or more prior lines of therapy, the ORR was 78.6%, with 14.3% achieving CR and 64.3% PR. Organ-specific response rates were as follows: joints, 100.0%; oral cavity, 90%; liver, 75.0%; skin, 71.4%; eyes, 60.0%; lungs, 60.0%; and gastrointestinal tract, 50.0%. At 3 and 6 months post-treatment, 41.2% (n = 7 ) and 75.0% (n = 12) of patients reported significant symptom improvement, respectively, and were defined as a ≥7-point reduction in LSS scores in their last follow-up. Two treatment failures were reported: one case of leukemia ( the patient had active leukemia before allo-HSCT, experienced recurrence post-transplant, and underwent multiple strategies against relapse, including 3 times of donor lymphocyte infusions; severe acute GVHD and extensive cGVHD were also present) relapsed after 8 weeks of belumosudil. The other case of cGVHD progression after 4 weeks of belumosudil, and ruxolitinib was added for this patient as a combination strategy. There was no recurrence of their primary malignant diseases for the rest 16 patients. No new infections occurred during the application of belumosudil treatment. No serious AEs (grade >3) were reported, and 10 patients experienced side effects, including asthenia (n = 3), nausea or vomiting (n = 2), and moderate kidney failure (n = 1), all these AEs were grade 1-2.

Conclusion: This real-world study demonstrates that belumosudil is efficacious, well-tolerable, and safe for recipients with cGVHD persisting for at least 2 years after diagnosis and following multiple lines of anti-cGVHD therapy. Most patients exhibit meaningful clinical improvement with belumosudil. No significant increase in the risk of disease recurrence or infection was observed. These findings support belumosudil as an effective therapeutic option for cGVHD in both advanced-stage and heavily pretreated settings. Further studies with larger sample sizes are warranted to validate these preliminary findings.

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2025
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