Symposium | Current treatment options for SR-cGvHD

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).

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 

• 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 

• 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 

• 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)

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 

This educational resource is independently supported by Sanofi. All content is developed by the faculty in collaboration with SES. Funders are allowed no influence.