Belumosudil in the treatment of steroid-refractory chronic graft-versus-host disease in children: the combined experience of nine centers of the Russian Federation

Introduction. Chronic graft-versus-host disease (cGVHD) remains a serious complication of allogeneic hematopoietic stem cell transplantation in children. In steroid-refractory cases, the prognosis is still unfavorable, and data on the use of the selective ROCK2 inhibitor belumosudil in the pediatric population, particularly in children under 12 years of age, are limited.

Materials and methods. A retrospective multicenter analysis was conducted on 43 patients aged ≤ 18 years with steroid-refractory or steroiddependent cGVHD (2014 NIH criteria) who received belumosudil in 9 transplant centers across the Russian Federation between 2023 and 2025. The dose of the drug was determined by the patient's body weight, ranging from 50 to 200 mg/day. The evaluation included the rate and speed of achieving an overall response (complete and partial responses), organ-specific efficacy, safety profile, as well as the frequency of dose reduction, temporary interruptions, and treatment discontinuation.

Results. The median age of patients at the start of therapy was 12 years (range: 2–18 years). The median number of prior lines of therapy was 3.

An overall response was achieved in 65 % of patients (28/43): a complete response in 5 % (2/43) and a partial response in 60 % (26/43). The highest rates of organ-specific responses were observed in lung involvement (79.5 %), gastrointestinal tract (64 %), oral mucosa, and eyes (65.5 % and 68.5 %, respectively). The median time to response was 35 days. Adverse events of any grade were reported in 70 % of patients, with serious events occurring in 37 %. The most frequent were infectious complications (56 %), hematological toxicity (37 %), and hepatotoxicity (21 %). Dose reduction was required in 35 % of patients, a temporary interruption in 21 %, and treatment discontinuation in 19 %.

Conclusion. Belumosudil demonstrated clinically significant efficacy and a manageable safety profile in pediatric patients with severe steroid-refractory cGVHD, including children under 12 years of age. The data obtained add to the limited global publications on the use of belumosudil in pediatrics and support the feasibility of conducting prospective studies.

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