How can ECP be positioned in the current GvHD treatment landscape as a steroid-free intervention?

The GvHD Hub was pleased to speak with Robert Zeiser, University of Freiburg, Freiburg, DE. We asked, How can ECP be positioned in the current GvHD treatment landscape as a steroid-free intervention? 

In this interview, Zeiser discusses the potential positioning of extracorporeal photopheresis (ECP) in the treatment landscape of acute graft-versus-host disease (aGvHD) and chronic GvHD (cGvHD), noting that corticosteroids remain the standard first-line treatment in both settings. He highlights the steroid-sparing potential of ECP and considers its role as a second- or later-line treatment option, either alone or in combination with other agents, including ruxolitinib. He also emphasizes the need for further prospective studies to clarify the optimal sequencing of ECP and its use in combination with other therapies.  

Key points 

aGvHD 

• Corticosteroids are the standard first-line treatment for aGvHD, while ruxolitinib is an established second-line option.¹ 
• In the ruxolitinib group of the phase III REACH-2 trial, the response rate in patients with steroid-refractory (SR)-aGvHD decreased from 62% at Day 28 to 40% at Day 56, highlighting an unmet need for approaches that provide more durable disease control in this population.² 
• Results from a retrospective study of 78 patients with SR-aGvHD demonstrated that combining ruxolitinib with ECP provides improved long-term control of aGvHD and less cGvHD at 1 year compared with ruxolitinib alone.³ 
• ECP is a valuable steroid-sparing approach in SR-aGvHD, with a systematic review and meta-analysis of 38 studies reporting that steroid tapering was possible in 66% of patients receiving ECP.⁴ 
• These findings support consideration of ECP, in combination or in sequence with ruxolitinib, as a potential second-line or later treatment strategy for patients with an inadequate response to ruxolitinib monotherapy and for whom steroid sparing is a priority. 

cGvHD 

• In patients with cGvHD refractory to first-line corticosteroids, ECP is an effective and well-tolerated steroid-sparing treatment option that may be positioned as an alternative to ruxolitinib in the second-line setting.^5,6 
• ECP does not induce generalized immunosuppression and has not been associated with an increased risk of infections, making it a potential treatment option for patients with infectious complications, in whom ruxolitinib may be less suitable.^5,7–9 
• Prospective data on the combined use of ECP and ruxolitinib remain limited; however, several retrospective studies have reported encouraging response rates and a favorable safety profile with this combination in cGvHD.^10–12 
• ECP may be considered as an alternative third-line treatment option for patients with cGvHD who are refractory to or ineligible for belumosudil, which is typically avoided in patients with moderate or severe hepatic impairment.^13–15 
• Although ECP plus belumosudil has demonstrated efficacy in cGvHD, further investigation is needed to determine the potential additive benefit of this combination.^16,17 
• There is currently no consensus on the optimal use of ECP across cGvHD manifestations, although several studies have reported higher response rates in the skin, gastrointestinal tract, liver, and oral mucosa.^18–20 

In summary, ECP is an effective and well-tolerated treatment option for GvHD and may be well positioned as a steroid-sparing approach in patients with aGvHD and cGvHD refractory to first line treatment, either as monotherapy or in combination with another agent with a different mechanism of action. 

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