ECP + ruxolitinib to prevent cGvHD in patients with SR-aGvHD

During the GvHD Hub Steering Committee Meeting on May 12, 2025, key opinion leaders met to discuss the use of extracorporeal photopheresis + ruxolitinib to prevent cGvHD in patients with SR‑aGvHD. The discussion was preceded by a presentation by Nico Gagelmann, chaired by Mohamad Mohty, and featured Robert Zeiser, Bipin Savani, Daniel Wolff, Corey Cutler, and Andrew Harris. 

Gagelmann began by presenting the design and rationale of a real-world retrospective study in Germany, response and survival outcomes, and key takeaways. 

Presentation 

Background

First-line treatment of GvHD is systemic, high-dose glucocorticoids; however, responses can vary, and glucocorticoids are associated with reduced quality of life and significant side effects. Loss of response can lead to SR-GvHD. Therefore, there is a need for effective second-line options.¹

Ruxolitinib, a JAK1/JAK2 inhibitor, is approved in the US and Europe for the treatment of aGvHD and cGvHD in patients with inadequate response to corticosteroids or other systemic therapies.^2,3 ECP is an immunomodulatory apheresis procedure that is recommended as a second-line (or later) treatment for cGvHD, although it is not yet approved.⁴

Study

A German retrospective study (Figure 1) was initiated to investigate the efficacy of ECP + ruxolitinib vs ruxolitinib alone in patients with SR-aGvHD treated between 2015 and 2022, and compare duration of response.⁵ The primary objective was overall response rate (ORR), including complete and partial response at Day 28.⁵

At Day 28, the CR rate was higher in the ruxolitinib group vs ECP + ruxolitinib. However, at Months 6 and 12, response rates were higher for ECP + ruxolitinib compared with ruxolitinib alone (Figure 2)⁵.

There was no difference in 1-year non-relapse mortality (NRM) and 2-year overall survival (OS) between groups, but ECP + ruxolitinib showed a significant cGvHD/relapse-free survival benefit vs ruxolitinib alone (27% vs 8% at 1-year).⁵

Discussion

• Combination therapies should be considered in the treatment of SR-GvHD due to the loss of response over time with monotherapies and the need to taper immunosuppressive drugs, including ruxolitinib.

• Previously, studies have demonstrated that ECP and ruxolitinib combination use in cGvHD resulted in improved patient response. Therefore, combining ruxolitinib with less toxic agents, such as ECP, is a promising approach.

• Limitations of this study include the retrospective and non-randomized nature; therefore, further studies of ECP + ruxolitinib could utilize a single- vs double-agent randomization approach.

• In higher-risk patients, initial response rate may not be an appropriate primary endpoint, and instead long-term efficacy data should be measured. This could be utilized for future trials of this combination.

• The combination of ECP + ruxolitinib shows promise for patients refractory to steroids and could provide longer-term response without compromising safety.

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