Ruxolitinib in Glucocorticoid-Refractory Acute Graft-vs-Host Disease After Stem Cell Transplant

Get Permission

In the phase III REACH2 trial reported in The New England Journal of Medicine, Zeiser et al found that the JAK1/2 inhibitor ruxolitinib improved response rate vs investigator’s choice of therapy in patients with glucocorticoid-refractory acute graft-vs-host disease (GVHD) following allogeneic stem cell transplantation (ASCT).

Study Details

In the open-label trial, 309 patients aged ≥ 12 years from sites in 22 countries were randomly assigned between April 2017 and May 2019 to receive ruxolitinib at 10 mg twice daily (n = 154) or investigator’s choice of therapy from a list of nine commonly used options (control group, n = 155) for up to 24 weeks. Treatment options in the control group included antithymocyte globulin, extracorporeal photopheresis, mesenchymal stromal cells, low-dose methotrexate, mycophenolate mofetil, an mTOR inhibitor (everolimus or sirolimus), etanercept, or infliximab; the most commonly used therapy was extracorporeal photopheresis (27% of control group).

The primary endpoint was overall response of GVHD at day 28. The key secondary endpoint was durable overall response at day 56.



  • Response rates at day 28 were 62% with ruxolitinib vs 39% with investigator’s choice of therapy.
  • Durable response at day 56 was observed in 40% vs 22% of patients.

Response at day 28 was observed in 96 patients (62%) in the ruxolitinib group vs 61 patients (39%) in the control group (odds ratio [OR] = 2.64, P < .001), with complete response observed in 53 patients (34%) vs 30 patients (19%). Response rates were 75% vs 51% among patients with grade II acute GVHD, 56% vs 38% among those with grade III acute GVHD, and 53% vs 23% among those with grade IV acute GVHD.

Durable response at day 56 was observed in 40% vs 22% of patients (OR = 2.38, P < .001). The estimated cumulative incidence of loss of response at 6 months was 10% vs 39%. Median failure-free survival was 5.0 months vs 1.0 month (hazard ratio [HR] for relapse or progression of hematologic disease, non-relapse­­–related death, or addition of new systemic therapy for acute GVHD = 0.46, 95% confidence interval [CI] = 0.35–0.60). Median overall survival was 11.1 months vs 6.5 months (HR = 0.83, 95% CI = 0.60–1.15).

Adverse Events

Through day 28, the most common adverse events reported were thrombocytopenia, which occurred in 33% of the ruxolitinib group vs 18% of the control group (grade ≥ 3 in 27% vs 15%), anemia (30% vs 28%), and cytomegalovirus infection (26% vs 21%). Grade ≥ 3 infection occurred in 22% vs 19% of patients. Serious adverse events occurred in 38% vs 34%.

The investigators concluded, “Ruxolitinib therapy led to significant improvements in efficacy outcomes, with a higher incidence of thrombocytopenia, the most frequent toxic effect, than that observed with control therapy.”

Disclosure: The study was funded by Novartis. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.