What factors drive your decision to switch from first- to second-line therapy for cGvHD?

The GvHD Hub was pleased to speak with Daniel Wolff, University Hospital Regensburg, Regensburg, DE. We asked, What factors drive your decision to switch from first- to second-line therapy for chronic graft-versus-host disease (cGvHD)? 

In this interview, Wolff discusses factors guiding his decision to escalate from first-line corticosteroids to second-line therapy in cGvHD. When considering a treatment switch, both efficacy and tolerability of steroid therapy should be evaluated, alongside consideration of other patient-related factors such as age, organ involvement, and infectious complications. 

Key points 

• Corticosteroids are the standard first-line treatment for cGvHD and are sometimes used in combination with other agents, including calcineurin inhibitors, mammalian target of rapamycin (mTOR) inhibitors, rituximab, or extracorporeal photopheresis.^1–3 
• When evaluating a switch to second-line treatment, response to corticosteroids should be assessed with respect to both therapeutic efficacy and tolerability:^4–7  
• Progression 
  • If a patient's condition continues to worsen or shows evidence of progression after 1–2 weeks of steroids (i.e. prednisone ≥1 mg/kg/day), the patient may be deemed steroid-refractory, and a switch to second-line treatment should be considered. 
  • Patients who cannot successfully taper corticosteroids without recurrence or progression of cGvHD (steroid-dependent disease) may also warrant transition to second-line treatment. 
  • In the absence of clear disease progression, the initial assessment of treatment response should be performed 4 weeks after initiation of steroids. 
• Stable disease 
  • If no meaningful clinical improvement is observed after 4 weeks of steroids (i.e. ≥0.5 mg/kg/day), it is important to consider whether a response is expected with continued steroid treatment. Persistent stable disease at this dose may also meet criteria for steroid-refractory cGvHD. 
  • For patients with a low symptom burden who are receiving a low steroid dose and experiencing minimal treatment toxicity, continued treatment may be appropriate. By contrast, patients with a high symptom burden or significant treatment-related toxicity may warrant an earlier transition to the next line of therapy.  
  • In general, a switch to second-line treatment may be considered after approximately 3 months of stable disease after initiation of steroids. 
• Partial response 
  • Partial response should be evaluated approximately 6 months after initiation of steroids. If residual disease remains and there is a reasonable expectation that an alternative therapy could further improve outcomes and enable complete remission, a switch to another treatment may be considered.
• Patient-specific factors may also inform treatment escalation: 
  • In pediatric patients, concerns regarding growth and developmental toxicities associated with prolonged high-dose steroid exposure may favor an earlier switch to second-line therapy.^2,8 
  • Likewise, older patients are at increased risk of steroid-related adverse effects, which may justify a lower threshold for transitioning to second-line therapy.^2,9 
  • Organ involvement may also guide treatment decisions, particularly with high-risk organ manifestations such as pulmonary GvHD, where disease progression can lead to irreversible damage and warrants close monitoring and timely escalation before significant loss of lung function occurs.^4,6,10,11 
  • The development of infectious complications may also influence the decision to transition to second-line therapy.² 
• Ruxolitinib, a Janus kinase 1/2 inhibitor, is the most broadly adopted second-line agent following European Medicines Agency approval, although it may not be suitable for patients with infectious complications.¹² 

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.