Potential therapeutic implications of early ECP for managing inflammation and limiting fibrosis in SOT

The SOT Hub spoke with Thomas Wekerle, Medical University of Vienna, AT. We asked about the therapeutic implications of early extracorporeal photopheresis (ECP) use for modulating inflammation and potentially limiting fibrotic progression in solid organ transplantation (SOT). 

In this interview, Wekerle discusses the potential for early ECP to modulate alloimmune responses and reduce the risk of chronic lung allograft dysfunction (CLAD) following lung transplantation. Drawing on clinical and preclinical evidence, he explores whether the long-term benefits observed with early ECP could be linked to effects on transforming growth factor-β (TGF-β)-mediated fibrotic pathways. Wekerle also discusses the favorable safety findings reported in a randomized trial and the need for further research to establish optimal treatment timing, duration, and patient selection. 

Key points 

• In a single-center, prospective randomized controlled trial, early use of ECP, initiated 1‒2 days after transplantation and continued for ~3 months alongside standard triple immunosuppression, reduced the number of acute cellular rejection (ACR) episodes and was associated with a lower incidence of CLAD compared with standard triple immunosuppression alone (the control group).¹ 
  • Freedom from high-grade ACR at 24 months was 97% with ECP vs 80% in the control group (p = 0.045). 
  • Competing-risk analysis showed a lower cumulative incidence of ACR with ECP vs control (p = 0.047). 
  • Freedom from CLAD at 1 year and 3 years was 100% and 85%, respectively, in the ECP group, compared with 86% and 71%, respectively, in the control group (p = 0.015), with a lower cumulative incidence of CLAD also observed in the ECP group. 
  • Rates of infection were lower in the ECP group compared with the control group (p = 0.001). 
• These findings suggest that a short course of ECP early after transplantation may have sustained clinical benefits.¹ 
• Persistent alloimmune inflammation may contribute to fibrotic progression by sustaining graft injury and promoting tissue remodeling; earlier control of inflammation may therefore represent a potential strategy for limiting ongoing injury and subsequent profibrotic processes.^2,3,4 
• Preclinical findings suggest that ECP may influence fibrotic pathways beyond its effects on alloimmune responses.⁴ 
  • In a mouse lung-transplant model, ECP inhibited the development of bronchiolitis obliterans syndrome (BOS) by modulating alveolar macrophage responses to transforming growth factor-β (TGF-β), a key regulator of fibrogenesis.⁵ 
• In summary, early ECP may provide sustained clinical benefits following lung transplantation.¹ Wekerle highlights that further research is needed to establish optimal treatment timing, duration, and patient selection. 

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