Long-term outcomes with ruxolitinib + ECP in SR-aGvHD

Although allogeneic hematopoetic stem cell transplant is potentially curative for patients with hematological malignancies, the development of acute graft-versus-host disease (aGvHD) remains a major limitation.¹ Glucocorticoids are the standard first-line treatment of aGvHD and chronic GvHD (cGvHD); however, not all patients respond to treatment.¹  

Ruxolitinib, a JAK1/2 inhibitor, is approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for patients with aGvHD and cGvHD.^2–4 In the REACH2 trial (NCT02913261), in patients with aGvHD treated with ruxolitinib, overall response rates decreased from 62% at Day 28 to 40% at Day 56, suggesting long-term disease control remains an unmet need.^1,5 Combination therapies are of clinical interest to address this, with initial studies underway. Extracorporeal photophoresis (ECP), a leukapheresis-based procedure, is an established treatment for steroid-refractory (SR-) GvHD, and, recently, Lastovytska et al. conducted a retrospective study to investigate the efficacy of ruxolitinib + ECP vs ruxolitinib alone in patients with SR-aGvHD treated between 2015 and 2022.^1,6  

Patients (N = 78) received oral ruxolitinib and steroid therapy followed by either ruxolitinib alone or ruxolitinib + ECP.¹ Response rates at 6 and 12 months were higher with ruxolitinib + ECP than with ruxolitinib alone, suggesting improved long-term control of aGvHD. Furthermore, while there was no difference in 1-year non-relapse mortality and 2-year overall survival between treatment groups, a significant cGvHD relapse-free survival benefit was observed with ruxolitinib + ECP vs ruxolitinib alone.  

Limitations of this study include the retrospective nature, delay of ECP initiation in some patients (the median time between ruxolitinib and initiating ECP was 9 days), and imbalance of GvHD severity between the two treatment arms (Grade 4 SR-aGVHD was 45% in the ruxolitinib + ECP group vs 14% with ruxolitinib alone, p < 0.001). Despite this, combining ruxolitinib + ECP shows promise for the treatment of SR-aGvHD, with improved control of aGvHD and less cGvHD at one year compared with ruxolitinib alone.¹ 

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