How do you approach later-line sequencing in cGvHD in your clinical practice?

The GvHD Hub was pleased to speak with Corey Cutler, Dana-Farber Cancer Institute, Boston, US. We asked, How do you approach later-line sequencing in chronic graft-versus-host disease (cGvHD) in your clinical practice?  

In this interview, Cutler discusses his approach to selecting second-line and subsequent therapies for patients with cGvHD. He explains that, in his practice, treatment selection is guided primarily by U.S. Food and Drug Administration (FDA) approval status and toxicity profiles, while organ involvement plays a more limited, context-dependent role. He highlights patient comorbidities and practical considerations, such as route of administration and dosing frequency, as additional factors that may influence therapy selection. 

 Key points

• Several factors should be considered when selecting second-line and subsequent therapies for cGvHD, including regulatory approval status, toxicity profile, and organ involvement.^1–3 
• Ibrutinib and ruxolitinib are approved by the FDA for the treatment of patients with cGvHD after ≥1 prior line of therapy (LoT); ruxolitinib is approved by the European Medicines Agency (EMA) for patients with cGvHD who have inadequate response to corticosteroids or other systemic therapies.^3–8 
  • Ruxolitinib is more commonly used in the second-line setting due to its favorable tolerability profile compared with ibrutinib. 
  • In patients with ongoing moderate-to-severe cytopenias, ibrutinib may be a preferable treatment option due to the risk of worsening cytopenias with ruxolitinib. 
  • Ibrutinib may also be considered in patients with underlying B-cell malignancies given its potential to prevent malignant relapse; however, evidence supporting this benefit remains limited. 
• Belumosudil and axatilimab are approved by the FDA for the treatment of patients with cGvHD after ≥2 prior LoT; belumosudil is approved by the EMA for patients with cGvHD who have exhausted all other treatment options.^3,8–14 
  • Belumosudil is frequently utilized in the third-line setting because of its oral administration and favorable tolerability; however, it is typically avoided in patients with moderate or severe hepatic impairment. 
  • In patients with very severe or active bronchiolitis obliterans, belumosudil is sometimes considered in the second-line setting based on anecdotal evidence suggesting potential reversal or improvement of bronchiolar changes. 
  • Axatilimab is more often reserved for fourth-line use, in part because it requires intravenous administration with biweekly dosing; it is generally avoided in patients with hepatic or pancreatic dysfunction, due to the potential for treatment-related worsening of these conditions. 
• Although antifibrotic and anti-inflammatory activity has been reported with both belumosudil and axatilimab,^13,15–17 Cutler notes that specific cGvHD manifestations and organ involvement alone do not typically guide treatment selection in his practice, as there is no reliable way to target therapy to specific organ manifestations. Instead, therapy choice is primarily driven by toxicity profiles and adherence to regulatory labeling. 

This educational resource is independently supported by Sanofi. All content is developed by SES in collaboration with an expert steering committee. Funders are allowed no influence.