Symposium | Emerging treatment strategies 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 Zinaida Perić, University of Rijeka, HR, outlining emerging treatment strategies for steroid-refractorychronic graft-versus-host disease (SR-cGvHD).

Perić highlights the growing shift toward targeted approaches that directly address the inflammation and fibrosis associated with cGvHD. She reviews the latest clinical data for several novel agents and combination approaches under evaluation for the treatment of SR-cGvHD, while emphasizing the need for larger-scale studies to confirm clinical benefit.

Key points

• Current therapies for SR-cGvHD demonstrate variable and often suboptimal efficacy, with reported response rates from 30% to 85%, highlighting the limitations of non-specific approaches.¹
• Treatment is increasingly shifting toward targeted and better-tolerated approaches that directly address the inflammatory and fibrotic mechanisms underlying cGvHD while minimizing broad immunosuppression.¹
• Belumosudil is approved by the U.S Food and Drug Administration (FDA) and received conditional marketing authorization from the European Commission in March 2026, expanding third-line treatment options for patients with SR-cGvHD.^2,3
• Several emerging agents and combinations are under investigation for the treatment of SR-cGvHD (Table 1).^4–13

Emerging agents

• Rovadicitinib (TQ05105) is a dual Janus kinase (JAK) 1/2 and Rho-associated kinase (ROCK) 1/2 inhibitor that has been evaluated in patients with moderate/severe SR or steroid-dependent (SD) cGvHD (N = 44) in a phase Ib/IIa study (NCT04944043; Figure 1).⁴

• TDI01 is a second-generation ROCK2 inhibitor that has been evaluated in a phase Ib/II study (NCT06169722) in patients with moderate/severe cGvHD after one to five prior lines of therapy (LoT; N = 60).⁵
  • The best overall response rate (ORR) was 75% in the 200 mg cohort and 86.2% in the 400 mg cohort.
  • Grade ≥3 treatment-emergent adverse events (TEAEs) and treatment-related AEs were reported in 51.7% and 38.3% of patients, respectively.
• Vimseltinib is a novel colony-stimulating factor 1 receptor (CSF-1R) inhibitor approved by the FDA and European Medicines Agency for the treatment of adults with tenosynovial giant cell tumor.^14,15
  • Based on its manageable safety profile, vimseltinib is now being evaluated in a phase II study in patients with cGvHD (NCT06619561).⁶
• Pimicotinib, another CSF-1R inhibitor, has been evaluated in a phase II study (NCT06186804) in adults with cGvHD after ≥1 prior LoT (N = 28).⁷
  • The 6-month ORR was 57.7% (66.7% in patients with moderate cGvHD; 52.9% in patients with severe cGvHD). 
  • TEAEs, Grade ≥3 TEAEs, and serious TEAEs occurred in 78.6%, 35.7%, and 21.4% of patients, respectively.

Combination approaches

• Given that inflammation and fibrosis often coexist in cGvHD, combining agents with complementary mechanisms of action may enable broader disease control, deeper responses, and reduced steroid exposure.^11,16,17
• The combination of axatilimab + ruxolitinib and/or belumosudil has been evaluated in a retrospective, single-center study in patients with severe, treatment-refractory cGvHD (N = 8).¹⁷
  • The ORR at any time was 25% per 2014 National Institute of Health consensus criteria and 75% per Clinically Significant Symptomatic Improvement as deemed by the provider.
  • Three Grade 3 serious AEs (osteomyelitis, septic arthritis, and elevated gamma-glutamyl transferase level) occurred in a single patient.
• Belumosudil + ruxolitinib has also been investigated in a retrospective, observational study in patients with SR-cGvHD (N = 26), reporting numerically higher mean ORR across most organ systems (except skin and gastrointestinal tract) compared with belumosudil + a standard agent (Figure 2).¹⁸
  • Belumosudil + ruxolitinib appeared to be well tolerated without excess toxicity.

• Extracorporeal photopheresis (ECP) + ruxolitinib has been evaluated in patients with SR-cGvHD in a retrospective, single-center study (N = 23), showing a best response at any time of 74% (complete response, 9%; partial response, 65%).¹⁹
  • Cytomegalovirus reaction and cytopenia occurred in 26% and 48% of patients, respectively.
• ECP in combination with low-dose interleukin-2 or belumosudil has also been investigated in patients with cGvHD.^20,21
• Larger-scale studies are needed to confirm benefit and long-term outcomes of these emerging strategies in patients with 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.