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Daniel WolffDo you know... Which of the following situations would indicate that a switch to third-line treatment for cGvHD should be considered?
During the 8th International Chronic Graft-versus-Host Disease Symposium, the GvHD Hub held a live symposium on May 22, 2026, titled “Evolving treatment strategies in SR‑cGvHD: Optimizing patient selection across current and emerging therapies”. Here, we share a presentation by Daniel Wolff, Regensburg, DE, outlining treatment options for steroid-refractory chronic graft-versus-host disease (SR-cGvHD).
Symposium | Current treatment options for SR-cGvHD
Symposium | Current treatment options for SR-cGvHD
Wolff reviews available therapeutic options for SR-cGvHD, including key data from pivotal trials of approved and widely adopted therapies. He discusses indications for transitioning to second- and third-line treatments, outlines his approach to managing SR-cGvHD, and highlights remaining unmet treatment needs.
Key points
- cGvHD is a major cause of late morbidity, occurring in 30–50% of patients who undergo allogenic hematopoietic stem cell transplantation.1–4
- Quality of life is significantly impaired in patients with cGvHD, and although corticosteroids remain the standard first-line treatment, long-term use is associated with significant toxicity.5–7
- Approximately 50% of patients with cGvHD become refractory to or dependent on steroids, and patients with SR-cGvHD have significantly increased morbidity and mortality. Therefore, there is a major unmet need for novel, steroid-sparing approaches to cGvHD treatment.6,7
- Several treatment options are approved for the management of SR-cGvHD (Figure 1), including ibrutinib (a Bruton’s tyrosine kinase inhibitor), belumosudil (a Rho-associated kinase 2 inhibitor), ruxolitinib (a Janus kinase 1/2 inhibitor), and axatilimab (a colony-stimulating factor receptor blocking monoclonal antibody), with data from several pivotal trials supporting their approval (Figure 2).6,8–15
Figure 1. Current treatment options for SR-cGvHD: Approval timeline*
Figure 2. Summary of pivotal trials of approved therapies for SR-cGvHD*
- Although not approved, extracorporeal photophoresis (ECP) is a widely adopted therapy for SR-cGvHD.
- In a single-center study of patients with cGvHD treated with ECP (n = 87) or no ECP (n = 202), 6-month overall response rate was 76% in patients treated with ECP vs 68% in patients with no ECP. Response did not differ when ECP was used before, concomitant with, or after ruxolitinib and/or belumosudil.16
- Despite available treatment options, clinical outcomes in SR-cGvHD remain sub-optimal.
- Treatment effectiveness varies depending on the type of cGvHD manifestation and the affected organs (inflammatory [i.e., skin, liver] vs fibrotic [i.e., lung, skin]).6,17,18
- Real-world data suggest that fibrotic manifestations, including lung involvement, show lower responses to ruxolitinib and may therefore require alternative therapies.19,20
- Response to first-line steroid treatment can indicate whether second-line treatment should be considered (Figure 3).4,21
Figure 3. Indications for second-line treatment of SR-cGvHD*
- There are various factors that may arise during assessment of patients that signal a change of treatment could be required. Examples include increases in National Institute of Health (NIH) scores (skin, eyes, and oral), loss of photographic range of motion ≥1 or progression by NIH grade (fascia), or drop of forced expiratory volume in 1 second >10% in the absence of infection (lung). 4,21,22
- Response to second-line treatment can also indicate whether third-line treatment should be considered (Figure 4).4,21,23
Figure 4. Indications for third-line treatment of SR-cGvHD*
- When proceeding with third-line treatment, it is recommended to avoid switching more than one drug at once (except in patients showing rapid progression), in order to facilitate identification of the effective agent.4
- Wolff provided a summary of his approach to treatment of SR-cGvHD (Figure 5).
Figure 5. Approach to treatment of SR-cGvHD
Ongoing unmet treatment needs
- Despite the investigation and approval of several steroid-sparing drugs in recent years, several unmet needs remain in the treatment of SR-cGvHD (Figure 6).4,24–28
Figure 6. Unmet needs in the treatment of SR-cGvHD*
This educational resource is independently supported by Sanofi. All content is developed by the faculty in collaboration with SES. Funders are allowed no influence.
References
Arai S, Arora M, Wang T, et al. Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: A report from the Center for International Blood and Marrow Transplant Research. Biol Blood Marrow Transplant. 2014;21(2):266-274. DOI: 10.1016/j.bbmt.2014.10.021
Arora M, Cutler CS, Jagasia MH, et al. Late acute and chronic graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2016;22(3):449-455. DOI: 10.1016/j.bbmt.2015.10.018
Velickovic VM, McIlwaine E, Zhang R, et al. Adverse events in second- and third-line treatments for acute and chronic graft-versus-host disease: Systematic review. Ther Adv Hematol. 2020;11:2040620720977039. DOI: 10.1177/2040620720977039
Wolff D, Schleuning M, von Harsdorf S, et al. Consensus conference on clinical practice in chronic GvHD: Second-line treatment of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2011;17(1):1-17. DOI: 10.1016/j.bbmt.2010.05.011
Yu J, Hamilton BK, Turnbull J, et al. Patient-reported symptom burden and impact on daily activities in chronic graft-versus-host disease. Cancer Med. 2023;12(3):3623-3633. DOI: 10.1002/cam4.5209
Karaszewski K, Sekuła M, Jędrzejczak WW. Optimal treatment of steroid-refractory chronic graft-versus-host disease (cGvHD) in the era of novel drugs - a systematic review and meta-analysis. Stem Cell Rev Rep. 2026;22(3):1341-1350. DOI: 10.1007/s12015-025-11046-9
Wolff D, Fatobene G, Rocha V, et al. Steroid-refractory chronic graft-versus-host disease: treatment options and patient management. Bone Marrow Transplantation. 2021;56:2079-2087. DOI: 10.1038/s41409-021-01389-5
Lee SJ, Zeiser R. FDA-approved therapies for chronic GvHD. Blood. 2025;145(8):795-800. DOI: 10.1182/blood.2024026633
Ruxolitinib. Summary of Product Characteristics (EMA). 2012.
Belumosudil. Summary of Product Characteristics (EMA). 2026.
Miklos D, Cutler CS, Arora M, et al. Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood. 2017;130(21):2243-2250. DOI: 10.1182/blood-2017-07-793786
Zeiser R, Polverelli N, Ram R, et al. Ruxolitinib for glucocorticoid-refractory chronic graft-versus-host disease. N Engl J Med. 2021; 385(3):228-238. DOI: 10.1056/NEJMoa2033122
Ayuk FA. Chronic GvHD: One more promising player enters the arena. Blood. 2025;145(24):2804-2807. DOI: 10.1182/blood.2025028751
Cutler C, Lee SJ, 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): 2278-2289. DOI: 10.1182/blood.2021012021
Wolff D, Cutler C, Lee SJ, et al. Axatilimab in recurrent or refractory chronic graft-versus-host disease. N Engl J Med. 2024;391(11):1002-1014. DOI: 10.1056/NEJMoa2401537
Solh MM, Bashey A, Morris LE, et al. Extracorporeal photopheresis (ECP) in the era of new chronic graft-versus-disease (GvHD) therapies. Blood. 2024;144(Suppl 1):4912. DOI: 10.1182/blood-2024-208659
Zeiser R, Blazar BR. Pathophysiology of chronic graft-versus-host disease and therapeutic targets. N Engl J Med. 2017;377(26):2565-2579. DOI: 10.1056/NEJMra1703472
Choe H, DeFilipp Z. Current therapeutics for sclerotic and fibrotic manifestations of chronic graft-versus-host disease. Bone Marrow Transplant. 2026;61:11-17. DOI: 10.1038/s41409-025-02743-7
Redondo S, Esquirol A, Novelli S, et al. Efficacy and safety of ruxolitinib in steroid-refractory/dependent chronic graft-versus-host disease: Real-world data and challenges. Transplant Cell Ther. 2022;28(1):43.e1-43.e5. DOI: 10.1016/j.jtct.2021.10.015
Wei C, Zhang X, Liang D, et al. Ruxolitinib for treatment of steroid-refractory graft-versus-host disease: Real-world data from chinese patients. Drug Des Devel Ther. 2021;15:4875-4883. DOI: 10.2147/DDDT.S338752
Schoemans HM, Lee SJ, Ferrara JL, et al. EBMT-NIH-CIBMTR Task Force position statement on standardized terminology & guidance for graft-versus-host disease assessment. Bone Marrow Transplant. 2018;53(11):1401-1415. DOI: 10.1038/s41409-018-0204-7
Lee SJ, 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):984-999. DOI: 10.1016/j.bbmt.2015.02.025
Dignan FL, Amrolia P, Clark A, et al. Diagnosis and management of chronic graft-versus-host disease. Br J Haematol. 2012;158(1):46-61. DOI: 10.1111/j.1365-2141.2012.09128.x
Malard F, Peric Z, Ruggeri A, et al. Chronic graft-versus-host disease: Current situation and unmet needs - A European position statement. Bone Marrow Transplant. 2026;61(4):373-384. DOI: 10.1038/s41409-026-02817-0
Hill GR, Betts BC, Tkachev V, et al. Current concepts and advances in graft-versus-host disease immunology. Ann Rev Immunol. 2021;39:19-49. DOI: 10.1146/annurev-immunol-102119-073227
Broers AEC, Meijer E, van der Holt B, et al. Time-restricted versus standard-duration immunosuppression after allogeneic hematopoietic stem cell transplantation: Results of the prospective randomized HOVON-96 trial. Hemasphere. 2024;8(12):e70040. DOI: 10.1002/hem3.70040
Fatoum H, Zeiser R, Hashmi SK. A personalized, organ-based approach to the treatment of chronic steroid-refractory graft-versus-host disease. Blood Reviews. 2024;63:101142. DOI: 10.1016/j.blre.2023.101142
Doering J, Perl M, Weber D, et al. Incidence and outcome of atypical manifestations of chronic graft-versus-host disease: Results from a retrospective single-center analysis. Transplant Cell Ther. 2023;29(12):772.e1-772.e10. DOI: 10.1016/j.jtct.2023.09.016
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