The combination of ruxolitinib with donor regulatory T cells (Treg) improved outcomes of chronic graft vs host disease (cGVHD) in animal models, supporting the initiation of a clinical trial among patients, according to the results of study published in the journal Scientific Reports.

Ruxolitinib is currently used for the treatment of refractory acute or chronic GVHD, and Tregs have demonstrated promise in this setting by modulating effector immune cells. Given that these therapies have shown efficacy separately, the aim of this study was to determine if the combination could further improve outcomes in a preclinical model.

The study evaluated the effect of ruxolitinib on Tregs in vitro using activated human peripheral blood mononuclear cells (PBMCs). Ruxolitinib increased the ratio of Treg to conventional T cells, whereas the population of conventional T cells increased in nonactivated control PBMCs. Treatment with ruxolitinib also decreased the expression of receptors that bind to inflammatory chemokines, with a greater effect observed on Tregs compared with conventional T cells.

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The combination of ruxolitinib and donor Tregs was evaluated in a progressive onset GVHD mouse model with established signs of acute and chronic GVHD. Animals were randomly assigned to receive a single infusion of Tregs plus daily administration of ruxolitinib, vehicle, a single treatment of ruxolitinib alone, or a single infusion of Tregs alone. Tissues were evaluated in most animals at 12 weeks after treatment initiation, whereas a subset underwent bone marrow biopsies up to 50 weeks.

The number of mice surviving was significantly higher in the combined treatment group compared with groups that received the vehicle controls (P =.0036) or ruxolitinib monotherapy (P =.0164). The survival rate of the group that received Tregs was lower than the combined treatment group, but this was not significant.

Acute and chronic GVHD clinical scores and weight loss were also significantly improved with the combination treatment compared with the groups treated with vehicle controls or either single therapy (P <.0001).

The infused Tregs persisted throughout the study, and were identified at the 50-week timepoint in bone marrow. The combined treatment of ruxolitinib plus Tregs also did not affect the efficacy of the graft on leukemia cells.

The authors concluded that they “have been able to determine that the combined treatment of GVHD with ruxolitinib and Treg, starting with the disease already established, can outperform the individual treatments.” A clinical trial of the addition of donor Tregs to patients with GVHD and a partial response to ruxolitinib is ongoing ( Identifier: NCT03683498).

Disclosures: This study was partially funded by Novartis. Please see the original reference for a full list of disclosures.


Rodríguez-Gil A, Escamilla-Gómez V, Nufer M, et al. Combined treatment of graft versus host disease using donor regulatory T cells and ruxolitinib. Sci Rep. 2022;12:8348. doi: 10.1038/s41598-022-12407-x