Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Real-world experience of belumosudil and belumosudil/ruxolitinib combination in steroid-refractory chronic graft-versus-host disease

Bone Marrow Transplantation (2025)Cite this article

Subjects

Abstract

Belumosudil is approved after failure of ≥2 lines of therapy in chronic graft-versus-host disease cGVHD. However, real-world data is limited. We conducted a retrospective analysis of 67 patients with steroid-refractory or dependent (SR/SD) cGVHD. At baseline, most patients had advanced multi-organ cGVHD. The 6- and 12-month overall response rate (ORR) was 61%. However, a subset of patients achieved deeper responses with ongoing therapy at 12 months. The 6-month failure-free survival (FFS) was 75% (95%CI: 65–86) whereas the 12-month FFS was 66% (95%CI: 55–78). A low incidence of drug-related grade ≥3 toxicities was observed. A cohort of patients with immune function analysis showed gradual improvement in immune subsets at 1-year post-treatment. The combined bel-rux cohort (n = 14) showed a 6- and 12-month ORR of 64% and 57%, respectively. Overall, belumosudil was associated with high treatment response and survival outcomes. Notably, deeper responses were observed with ongoing therapy, and it was overall well tolerated. In a cohort of patients, immune cell populations had preserved to improved values throughout treatment. Patients who received bel-rux demonstrated efficacy and safety as well. Overall, our real-world study indicates similar findings to the clinical trial and supports the use of belumosudil in cGVHD.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Organ-specific response.
Fig. 2: Belumosudil overall response rate (ORR) at 6- and 12-months.
Fig. 3: Failure-free survival (FFS).
Fig. 4: Overall survival (OS).
Fig. 5: Combined belumosudil-ruxolitinib treatment overall response rate (ORR).
Fig. 6: Lymphocyte subsets measurement over 1-year.

Similar content being viewed by others

Data availability

The datasets generated and analyzed during the current study are available from the corresponding author on a reasonable request.

References

  1. Zeiser R, Blazar BR. Pathophysiology of chronic graft-versus-host disease and therapeutic targets. N Engl J Med. 2017;377:2565–79.

    Article  CAS  PubMed  Google Scholar 

  2. Wong FL, Francisco L, Togawa K, Bosworth A, Gonzales M, Hanby C, et al. Long-term recovery after hematopoietic cell transplantation: predictors of quality-of-life concerns. Blood. 2010;115:2508–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Pidala J, Kurland B, Chai XY, Majhail N, Weisdorf D, Pavletic S, et al. Patient-reported quality of life is associated with severity of chronic graft-versus-host disease as measured by NIH criteria: report on baseline data from the Chronic GVHD Consortium. Blood. 2011;117:4651–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transpl. 2015;21:389–401.e381.

    Article  Google Scholar 

  5. Kitko CL, White ES, Baird K. Fibrotic and sclerotic manifestations of chronic graft-versus-host disease. Biol Blood Marrow Transpl. 2012;18:S46–52.

    Article  Google Scholar 

  6. MacDonald KP, Hill GR, Blazar BR. Chronic graft-versus-host disease: biological insights from preclinical and clinical studies. Blood. 2017;129:13–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Vadakkel G, Eng S, Proli A, Ponce DM. Updates in chronic graft-versus-host disease: novel treatments and best practices in the current era. Bone Marrow Transpl. 2024;59:1360–8.

    Article  Google Scholar 

  8. Baird K, Steinberg SM, Grkovic L, Pulanic D, Cowen EW, Mitchell SA, et al. National Institutes of Health Chronic Graft-versus-Host Disease Staging in Severely Affected Patients: Organ and Global Scoring Correlate with Established Indicators of Disease Severity and Prognosis. Biol Blood Marrow Transpl. 2013;19:632–9.

    Article  Google Scholar 

  9. Bolanos-Meade J, Hamadani M, Wu J, Al Malki MM, Martens MJ, Runaas L, et al. Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis. N Engl J Med. 2023;388:2338–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Arora M, Cutler CS, Jagasia MH, Pidala J, Chai X, Martin PJ, et al. Late Acute and Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transpl. 2016;22:449–55.

    Article  Google Scholar 

  11. Lee SJ, Wolff D, Kitko C, Koreth J, Inamoto Y, Jagasia M, 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 Transpl. 2015;21:984–99.

    Article  Google Scholar 

  12. Flowers MED, Martin PJ. How we treat chronic graft-versus-host disease. Blood. 2015;125:606–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Zanin-Zhorov A, Weiss JM, Nyuydzefe MS, Chen W, Scher JU, Depoil D, 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;111:16814–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Flynn R, Paz K, Du J, Reichencbach DK, Taylor PA, Panoskaltsis-Mortari A, et al. Targeted Rho-associated kinase 2 inhibition suppresses murine and human chronic GVHD through a Stat3-dependent mechanism. Blood. 2016;127:2144–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Cutler C, Lee SJ, Arai S, Rotta M, Zoghi B, Lazaryan A, et al. Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study. Blood. 2021;138:2278–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Riches DW, Backos DS, Redente EF. ROCK and Rho: Promising therapeutic targets to ameliorate pulmonary fibrosis. Am J Pathol. 2015;185:909–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Przepiorka D, Le RQ, Ionan A, Lii EJ, Qang YH, Gudi R, 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;28:2488–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Michonneau D, Malard F, Le Grand S, Magro L, D’Aveni M, Tudesq JJ, et al. Efficacy and safety of belumosudil for treatment of cGVHD: multicenter retrospective analysis of the French cohort of the compassionate use program, on behalf of the French Society of Bone Marrow Transplantation and Cellular Therapy. Bone Marrow Transpl. 2025;60:779–86.

    Article  CAS  Google Scholar 

  19. Modi B, Ngo D, Chen J, Yang D, Shan H, Sandhu K, et al. Belumosudil for the treatment of chronic graft-versus-host disease: a single center real-world experience. Bone Marrow Transpl. 2025;60:555–7.

    Article  Google Scholar 

  20. Heidenreich S, Egger-Heidrich K, Halter JP, Jost L, Stölzel F, Perl M, et al. Safety and efficacy of the ROCK-2-inhibitor Belumosudil in cGvHD treatment - a retrospective, German-Swiss multicenter real-world data analysis. Bone Marrow Transpl. 2025;60:439–46.

    Article  CAS  Google Scholar 

  21. Chin MM, Tamaresis JS, Johnston LJ, Lowsky R, Meyer E, Muffly L, et al. Belumosudil combination therapy for chronic graft-versus-host-disease in real-world clinical practice. Bone Marrow Transpl. 2025;60:393–5.

    Article  Google Scholar 

  22. Dierov D, Webb N, Fatmi S, Nwanne Cm Ciolino C, Mosesso K, et al. Establishing a standardized system for review and adjudication of chronic graft-vs-host disease data in accordance with the National Institutes Consensus criteria. Adv Cell Gene Ther. 2019;2:62.

  23. Schoemans HM, Lee SJ, Ferrara JL, Wolff D, Levine JE, Schultz KR, et al. EBMT-NIH-CIBMTR Task Force position statement on standardized terminology & guidance for graft-versus-host disease assessment. Bone Marrow Transpl. 2018;53:1401–15.

    Article  Google Scholar 

  24. Copelan E, Casper JT, Carter SL, van Burik JAH, Hurd D, Mendizabal AM, et al. A scheme for defining cause of death and its application in the T cell depletion trial. Biol Blood Marrow Transpl. 2007;13:1469–76.

    Article  Google Scholar 

  25. Keever-Taylor C, Devine S, Soiffer R, Mendizabal A, Carter S, Pasquini MC, et al. Characteristics of CliniMACS® System CD34-enriched T cell-depleted grafts in a multicenter trial for acute myeloid leukemia-Blood and Marrow Transplant Clinical Trials Network (BMT CTN) protocol 0303. Biol Blood Marrow Transpl. 2012;18:690–7.

    Article  Google Scholar 

  26. DeFilipp Z, Alousi AM, Pidala JA, Carpenter PA, Onstad LE, Arai S, et al. Nonrelapse mortality among patients diagnosed with chronic GVHD: an updated analysis from the Chronic GVHD Consortium. Blood Adv. 2021;5:4278–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Saidu NEB, Bonini C, Dickinson A, Grce M, Inngjerdingen M, Koehl U, et al. New Approaches for the Treatment of Chronic Graft-Versus-Host Disease: Current Status and Future Directions. Front Immunol. 2020;11:578314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Malard F, Huang XJ, Sim JPY. Treatment and unmet needs in steroid-refractory acute graft-versus-host disease. Leukemia. 2020;34:1229–40.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Wolff D, Radojcic V, Lafyatis R, Cinar R, Rosenstein RK, Cowen EW, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2020 Highly morbid forms report. Transpl Cell Ther. 2021;27:817–35.

    Article  Google Scholar 

  30. Lee SJ, Cutler C, Blazar BR, Tu A, Yang Z, Pavletic SZ. Correlation of Patient-Reported Outcomes with Clinical Organ Responses: Data from the Belumosudil Chronic Graft-versus-Host Disease Studies. Transpl Cell Ther. 2022;28:700 e701–700.e706.

    Article  Google Scholar 

  31. Inamoto Y, Kato K, Kawakita T, Onishi Y, Matsuoka KI, Shiratori S, et al. An open-label study of belumosudil, a selective ROCK2 inhibitor, as second or subsequent line of therapy for steroid-dependent/steroid-resistant chronic GVHD. Am J Hematol. 2024;99:1917–26.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The work was also supported in part by the Memorial Sloan Kettering Cancer Center Support Grant (P30 CA008748); National Institutes of Health award number 5R01-HL164902-02.

Author information

Authors and Affiliations

  1. Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Gagan Raju, Moneeza Walji, Ilan Goldstein, Amandeep Singh, Pamela Susman, Natasia Rodriguez, Miguel-Angel Perales & Doris M. Ponce

  2. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    David Nemirovsky & Sean Devlin

  3. Weill Cornell Medical College, New York, NY, USA

    Miguel-Angel Perales & Doris M. Ponce

Authors
  1. Gagan Raju
    View author publications

    Search author on:PubMed Google Scholar

  2. Moneeza Walji
    View author publications

    Search author on:PubMed Google Scholar

  3. David Nemirovsky
    View author publications

    Search author on:PubMed Google Scholar

  4. Sean Devlin
    View author publications

    Search author on:PubMed Google Scholar

  5. Ilan Goldstein
    View author publications

    Search author on:PubMed Google Scholar

  6. Amandeep Singh
    View author publications

    Search author on:PubMed Google Scholar

  7. Pamela Susman
    View author publications

    Search author on:PubMed Google Scholar

  8. Natasia Rodriguez
    View author publications

    Search author on:PubMed Google Scholar

  9. Miguel-Angel Perales
    View author publications

    Search author on:PubMed Google Scholar

  10. Doris M. Ponce
    View author publications

    Search author on:PubMed Google Scholar

Contributions

G.R., M.W., and D.M.P., designed the study, interpreted the data, and wrote the manuscript. D.N. and S.D. analyzed and interpreted the data and wrote the manuscript, I.G., A.S., P.M. collected the data, N.R. wrote the manuscript, M.A.P. interpreted the data and wrote the manuscript.

Corresponding author

Correspondence to Doris M. Ponce.

Ethics declarations

Competing interests

M.A.P reports honoraria from Adicet, Allogene, Allovir, Caribou Biosciences, Celgene, Bristol-Myers Squibb, Equilium, Exevir, ImmPACT Bio, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Nektar Therapeutics, Novartis, Omeros, OrcaBio, Sanofi, Syncopation, VectivBio AG, and Vor Biopharma. He serves on DSMBs for Cidara Therapeutics and Sellas Life Sciences, and the scientific advisory board of NexImmune. He has ownership interests in NexImmune, Omeros and OrcaBio. He has received institutional research support for clinical trials from Allogene, Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis. D.M.P. has served as advisory board member for Evive Biotechnology (Shanghai) Ltd; has consulted, received honorarium from, or participated in the advisory boards for Sanofi, Ceramedix, and Incyte Corporation, and received research funding from Sanofi and Incyte. The other authors have no conflicts of interest to declare.

Ethics approval

All methods were performed in accordance with the relevant guidelines and regulations. This analysis was approved by the Memorial Sloan Kettering Cancer Center Institutional Review Board (IRB #16-501; characterization of graft-versus-host disease following hematopoietic stem cell transplantation). Written informed consent for participation was obtained from all study participants.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Raju, G., Walji, M., Nemirovsky, D. et al. Real-world experience of belumosudil and belumosudil/ruxolitinib combination in steroid-refractory chronic graft-versus-host disease. Bone Marrow Transplant (2025). https://doi.org/10.1038/s41409-025-02721-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41409-025-02721-z

Search

Advanced search

Quick links