Ruxolitinib therapy appears to be more efficacious than commonly used treatments for glucocorticoid-refractory acute graft-vs-host disease (GVHD) in patients after allogeneic stem-cell transplantation (allo-SCT), according to results of the REACH2 trial published in The New England Journal of Medicine.

REACH2 ( Identifier: NCT02913261) was a multicenter, randomized, open-label, phase 3 trial that followed up on promising results from the REACH1 study ( Identifier: NCT02953678), in which 54.9% of the patients had a response to ruxolitinib, a selective Janus kinase (JAK1 and JAK2) inhibitor, after 28 days.

In REACH2, 309 patients (≥12 years of age) who had grade 2 to 4 glucocorticoid-refractory acute GVHD after allo-SCT were randomly assigned to receive oral ruxolitinib (10 mg twice/d; 154 patients) or the control (155 patients), which was the investigator’s choice of 9 commonly used therapies (antithymocyte globulin,

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extracorporeal photopheresis, mesenchymal stromal cells, low-dose methotrexate, mycophenolate mofetil, mammalian target of rapamycin inhibitor [everolimus or sirolimus], etanercept, or infliximab). The primary endpoint was overall response at day 28, and the key secondary endpoint was durable overall response at day 56.

Standard supportive therapy was permitted in both treatment groups, and patients in the control group were allowed to cross over to the ruxolitinib group at day 28 if they had no response or loss of response.

The overall response at day 28 was 62% in the ruxolitinib group and 39% in the control group (odds ratio [OR], 2.64; 95% CI, 1.65-4.22; P <.001). The durable overall response at day 56 was 40% in the ruxolitinib group and 22% in the control group (OR, 2.38; 95% CI, 1.43-3.94; P <.001).

The estimated cumulative incidence of loss of response at 6 months was lower in the ruxolitinib group (10%) than in control group (39%). The median failure-free survival was longer in the ruxolitinib group (5.0 months) than in the control group (1.0 month; hazard ratio [HR] for treatment failure, 0.46; 95% CI, 0.35-0.60). The median overall survival was also longer in the ruxolitinib group (11.1 months) than in the control group (6.5 months; HR for death, 0.83; 95% CI, 0.60-1.15).

According the authors, the safety profile of ruxolitinib was consistent with the known safety profile of ruxolitinib. Through day 28, the most common adverse events were thrombocytopenia (33% of the ruxolitinib group and 18% of the control group), anemia (30% and 28%, respectively), and cytomegalovirus infection (26% and 21%, respectively).

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“Little progress in the development of new treatments has been made in the past three decades,” wrote the authors. “This randomized, phase 3 trial showed a significant improvement with a new therapy over standard care in patients with grade II to IV glucocorticoid-refractory acute GVHD.”

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Zeiser R, von Bubnoff N, Butler J, et al. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. N Engl J Med. 2020;382(19):1800-1810.