Patients who develop glucocorticoid-refractory acute graft-versus-host disease (aGVHD) after allogeneic stem cell transplantation tend to have poor outcomes. Now, a new study published in The New England Journal of Medicine has found that ruxolitinib (Jakafi®) therapy may be associated with significantly higher overall response rates (ORRs) than standard therapy. Researchers conducted a phase 3 study with this selective Janus kinase (JAK1 and JAK2) inhibitor in patients with aGVHD and found significantly greater ORRs with ruxolitinib (62%) compared with best available therapy (BAT; 39%). 

THE STUDY

Ruxolitinib was approved by the US Food and Drug Administration (FDA) in 2019 for the treatment of steroid-refractory aGVHD in adult and pediatric patients aged 12 years or older. Researchers conducted a multicenter, randomized, open-label, phase 3 trial with 309 patients to compare the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator’s choice of therapy from a list of 9 commonly used options (control group). All the patients were age 12 or older and had developed glucocorticoid-refractory aGVHD after allogeneic stem cell transplantation (Safety and Efficacy of Ruxolitinib Versus Best Available Therapy in Patients With Corticosteroid-refractory Acute Graft vs Host Disease After Allogeneic Stem Cell Transplantation [REACH2]; ClinicalTrials.gov Number: NCT02913261).

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For this investigation, 154 patients were assigned to ruxolitinib and 155 were assigned to the control group. The primary endpoint was overall response (OR), which was defined as a complete response or partial response at day 28. Secondary endpoints included durable ORR at day 14, ORR at day 56, duration of response, overall survival (OS), and event-free survival.

All the patients were treated between April 12, 2017, and May 30, 2019, at 105 treatment centers in 22 countries. Median age was 54 years (range, 12 to 73), 59% were male, and 9 were adolescents. In this study, 34% of patients (104) had grade 2 aGVHD, 44% (136) had grade 3 disease, and 20% (62) had grade 4 disease.  The researchers evenly distributed patients according to aGVHD grade in the 2 treatment groups.