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.
Responses
KEY POINTS
- 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 nejm.org.
