Glucocorticoid-refractory acute graft-versus-host disease (GVHD) develops in approximately 50% of allogeneic stem-cell recipients and is a major cause of death.
A recently published phase 3 study indicated that ruxolitinib improved outcomes over other available therapies in patients with glucocorticoid-refractory acute graft-versus-host disease (GVHD).
Ruxolitinib is a selective Janus kinase (JAK1 and JAK2) inhibitor. The FDA approved ruxolitinib in 2019 for the treatment of steroid-refractory acute GVHD in adult and pediatric patients 12 years and older.
The multicenter, randomized, open-label trial compared the efficacy and safety of oral ruxolitinib (10 mg twice daily) with a control group. The results were published in The New England Journal of Medicine earlier this month.
In this study, the control group received the investigator’s choice of therapy from a list of 9 commonly used options: antithymocyte globulin, extracorporeal photopheresis, mesenchymel stromal cells, low-dose methotrexate, mycophenolate mofetil, mammalian target or rapamycin ihibitor (evrolimu or sirlolimus), etanercept, or infliximab.
Patients had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28. The key secondary end point was durable overall response at day 56.
GVHD develops in approximately 50% of allogeneic stem-cell recipients and is a major cause of death.
A total of 309 patients were randomized, with 154 patients assigned to the ruxolitinib group and 155 to the control group.
Overall response at day 28 was higher in the ruxolitinib group than in the control group (62% vs. 39%; odds ratio [OR], 2.64; 95% CI, 1.65 to 4.22; P <.001). Durable overall response at day 56 was higher in the ruxolitinib group than in the control group (40% vs. 22%; OR, 2.38; 95% CI, 1.43 to 3.94; P < .001). The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group and 39% in the control group.
The median failure-free survival was considerably longer with ruxolitinib than with control (5.0 months vs. 1.0 month). In addition, the hazard ratio (HR) for relapse or progression of hematologic disease, non—relapse-related death, or addition of new systemic therapy for acute GVHD was 0.46 (95% CI, 0.35 to 0.60).
The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (HR for death, 0.83; 95% CI, 0.60 to 1.15).
The most common adverse events up to day 28 were thrombocytopenia (33% in the ruxolitinib group and 18% in the control group), anemia (in 30% and 28%, respectively), and cytomegalovirus infection (26% and 21%).
No new safety signals were observed and adverse events (AEs) attributable to treatment were consistent with the known safety profile of ruxolitinib. The most common AEs were thrombocytopenia, anemia and cytomegalovirus infection.
The study was funded by Novartis.
Zeiser R, von Bubnoff N, Buter J, et al. Ruxolitinib for glucocorticoid-refractory acute graft-versus-host disease. N Engl J Med. 2020; 382:1800-1810 doi:10.1056/NEJMoa1917635.