Use of belumosudil for the treatment of chronic graft-versus-host disease
https://doi.org/10.35754/0234-5730-2026-71-2-202-209
Abstract
Chronic graft-versus-host disease (cGVHD) is one of the most significant late complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). First-line therapy is based on glucocorticosteroids; however, a substantial proportion of patients develop steroid-refractory disease requiring subsequent lines of treatment. In recent years, targeted therapies have been introduced into clinical practice, including belumosudil, a selective ROCK2 inhibitor.
Aim: to evaluate the efficacy and safety of belumosudil in patients with severe steroid-refractory cGVHD.
Main findings. In the presented case series, patients with severe cGVHD with lung involvement, refractory to glucocorticosteroids and prior therapies (including JAK inhibitors, antifibrotic, and immunomodulatory agents), received belumosudil as thirdor later-line treatment. Partial response was achieved in one patient, while disease stabilization was observed in two patients. In all cases, the treatment demonstrated a favorable safety profile, with no serious adverse events requiring discontinuation. These findings suggest that belumosudil is clinically effective in heavily pretreated patients, including those with advanced pulmonary involvement. However, the limited reversibility of fibrotic changes supports the rationale for earlier initiation of therapy.
About the Authors
V. A. Vasilyeva
National Medical Research Center for Hematology
Russian Federation
Russian Federation
Vera A. Vasilyeva, Cand. Sci. (Med.), Head of Outpatient Department for Immunochemotherapy after Bone Marrow and Hematopoietic Stem Cell Transplantation
125167, Moscow
O. M. Koroleva
National Medical Research Center for Hematology
Russian Federation
Russian Federation
Olga M. Koroleva, Hematologist of Outpatient Department for Immunochemotherapy after Bone Marrow and Hematopoietic Stem Cell Transplantation
125167, Moscow
L. A. Kuzmina
National Medical Research Center for Hematology
Russian Federation
Russian Federation
Larisa A. Kuzmina, Cand. Sci. (Med.), Hematologist, Head of Department of Chemotherapy for Hematological Malignancies and Bone Marrow and Hematopoietic Stem Cell Transplantation
125167, Moscow
References
1. MacDonald K.P.A., Hill G.R., Blazar B.R. Chronic graft-versus-host disease: biological insights from preclinical and clinical studies. Blood. 2017;129(1):13–21. DOI: 10.1182/BLOOD-2016-06-686618.
2. Arora M., Cutler C.S., Jagasia M.H., et al. Late Acute and Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2016;22(3):449–55. DOI: 10.1016/j.bbmt.2015.10.018.
3. Wong F.L., Francisco L., Togawa K., et al. Long-term recovery after hematopoietic cell transplantation: predictors of quality-of-life concerns. Blood. 2010;115(12):2508–19. DOI: 10.1182/BLOOD-2009-06-225631.
4. Lee S.J., Vogelsang G., Flowers M.E.D. Chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2003;9(4):215–33. DOI: 10.1053/bbmt.2003.50026.
5. Jagasia M., Lazaryan A., Bachier C.R., et al. ROCK2 inhibition with belumosudil (KD025) for the treatment of chronic graft-versus-host disease. J Clin Oncol. 2021;39(17):1888–98. DOI: 10.1200/JCO.20.02754;WGROUP:STRING:PUBLICATION.
6. Lee S.J., Nguyen T.D., Onstad L., et al. Success of Immunosuppressive Treatments in Patients with Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2018;24(3):555–62. DOI: 10.1016/j.bbmt.2017.10.042.
7. Moiseev I.S., Drokov M.Y., Motorin D. V., et al. Multicenter non-interventional retrospective study: prevalence, clinical characteristics and approaches to the treatment of acute and chronic graft-versus-host disease in the Russian Federation. Cell Ther Transplant. 2023;12(4):11–23. DOI: 10.18620/CTT-1866-8836-2023-12-4-11-23.
8. Zeiser R., Blazar B.R. Pathophysiology of Chronic Graft-versus-Host Disease and Therapeutic Targets. Longo DL, editor. N Engl J Med. 2017;377(26):2565–79. DOI: 10.1056/NEJMra1703472.
9. Moiseev I.S., Balashov D.N., Bronin G.O., et al. Recommendations of Russian Society for Hematopoietic Stem Cell Transplantation, Gene and Cell therapy for diagnosis and treatment of graft-versus-host disease. Cell Ther Transplant. 2025;14(2):55–86 (In Russian). DOI: 10.18620/CTT-1866-8836-2025-14-2-55-86.
10. DeFilipp Z., Couriel D.R., Lazaryan A., et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: III. The 2020 Treatment of Chronic GVHD Report. Transplant Cell Ther. 2021;27(9):729–37. DOI: 10.1016/j.jtct.2021.05.004.
11. Flowers M.E.D., Martin P.J. How we treat chronic graft-versus-host disease. Blood. 2015;125(4):606–15. DOI: 10.1182/BLOOD-2014-08-551994.
12. Zanin-Zhorov A., Weiss J.M., Nyuydzefe M.S., et al. Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism. Proc Natl Acad Sci USA. 2014;111(47):16814–9. DOI: 10.1073/PNAS.1414189111.
13. Flynn R., Paz K., Du J., et al. Targeted Rho-associated kinase 2 inhibition suppresses murine and human chronic GVHD through a Stat3-dependent mechanism. Blood. 2016;127(17):2144–54. DOI: 10.1182/BLOOD-2015-10-678706.
14. Cutler C., Lee S.J., Arai S., et al. Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study. Blood. 2021;138(22):2278–89. DOI: 10.1182/BLOOD.2021012021.
15. Lee S.J., Wolff D., Kitko C., et al. Measuring Therapeutic Response in Chronic Graft-versus-Host Disease. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2014 Response Criteria Working Group Report. Biol Blood Marrow Transplant. 2015;21(6):984–99. DOI: 10.1016/j.bbmt.2015.02.025.
16. Hall K., Lazaryan A., Der Laan M. van, et al. Efficacy and Safety of Belumosudil as Compared with Best Available Therapy for the Treatment of cGVHD in the US. Blood Adv. 2026;10 (3): 682-693. DOI: 10.1182/BLOODADVANCES.2025015832.
17. Bykova T.A., Levkovsky N. V., Moiseev I.S., et al. Belumosudil in pediatric patients with steroid-refractory chronic graft-versus-host disease: single-center experience. Cell Ther Transplant. 2025;14(2):35–40. DOI: 10.18620/CTT-1866-8836-2025-14-2-35-40.
18. Jagasia M.H., Greinix H.T., Arora M., et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graftversus-Host Disease: I. The 2014 Diagnosis and Staging Working Group Report. Biol Blood Marrow Transplant. 2015;21(3):389–401.e1. DOI: 10.1016/j.bbmt.2014.12.001.
19. Przepiorka D., Le R.Q., Ionan A., et al. FDA Approval Summary: Belumosudil For Adult and Pediatric Patients 12 Years and Older with Chronic GVHD After Two or More Prior Lines of Systemic Therapy. Clin Cancer Res. 2022;28(12):2488. DOI: 10.1158/1078-0432.CCR-21-4176.
20. Qadri M., Ihtasham A., Shahid I., et al. Efficacy and Safety of Belumosudil in Chronic Graft versus Host Disease (cGVHD): A Systematic Review and Meta-Analysis. Research Square 2025; DOI: 10.21203/RS.3.RS-6383341/V1.
21. Sharma R., Holtzman N.G., Pusic I., et al. Belumosudil reduces oral chronic graft-versus-host disease tissue infl ammation and fibrosis: a ROCKstar companion study. Blood Adv. 2025;9(14):3479–94. DOI: 10.1182/BLOODADVANCES.2025016170.
Review
For citations:
Vasilyeva V.A., Koroleva O.M., Kuzmina L.A. Use of belumosudil for the treatment of chronic graft-versus-host disease. Russian journal of hematology and transfusiology. 2026;71(2):202-209. (In Russ.) https://doi.org/10.35754/0234-5730-2026-71-2-202-209
Views:
74
JATS XML
Email this article 
