In the phase III REACH3 trial, reported in The New England Journal of Medicine, Robert Zeiser, MD, and colleagues found that ruxolitinib produced a significantly higher overall response rate vs investigator-selected control treatments in patients with glucocorticoid-refractory or -dependent chronic graft-vs-host disease (GVHD) after undergoing allogeneic stem cell transplantation.

Robert Zeiser, MD

Study Details

In the open-label trial, 329 patients aged ≥ 12 years from sites in 28 countries were randomly assigned between July 2017 and November 2019 to receive ruxolitinib at 10 mg twice daily (n = 165) or a control therapy selected by investigators from a prespecified list (n = 164). Control therapies available for selection included extracorporeal photopheresis, low-dose methotrexate, mycophenolate mofetil, mTOR inhibitors (everolimus or sirolimus), infliximab, rituximab, pentostatin, imatinib, or ibrutinib. Treatment was given for at least six 28-day cycles.

The primary endpoint was overall response (complete or partial response) at week 24, defined according to the 2014 National Institutes of Health consensus criteria. The most common underlying diseases were leukemia/myelodysplastic syndrome in 73% vs 74% and lymphoproliferative disorder in 16% vs 20% of patients.

Response Rates

Overall response rates at week 24 were 49.7% in the ruxolitinib group vs 25.6% in the control group (odds ratio [OR] = 2.99, 95% confidence interval [CI] = 1.86–4.80, P < .001), with complete response reported in 6.7% vs 3.0%. Overall response rates at week 24 were higher with ruxolitinib, irrespective of involved organs.

Among the trial’s secondary endpoints, symptom response at 24 weeks using the modified Lee Symptom Scale was achieved in 24.2% vs 11.0% of patients (OR = 2.62, 95% CI = 1.42–4.82, P = .001). At data cutoff (May 2020), median follow-up was 57.3 weeks. Median failure-free survival was not reached in the ruxolitinib group (> 18.6 months) vs 5.7 months in the control group (hazard ratio [HR] = 0.37, 95% CI = 0.27–0.51, P < .001).

Overall survival data were not mature at data cutoff. Median overall survival was not reached in either group (HR = 1.09, 95% CI = 0.65–1.82); estimated rates of survival at 12 months were 81.4% vs 83.8%.

Adverse Events

Grade ≥ 3 adverse events occurred in 57.0% of patients in the ruxolitinib group vs 57.6% of the control group, with the most common being thrombocytopenia (15.2% vs 10.1%), anemia (12.7% vs 7.6%), neutropenia (8.5% vs 3.8%), and pneumonia (8.5% vs 9.5%). Serious adverse events through week 24 occurred in 33.3% vs 36.7% of patients. Adverse events led to treatment discontinuation in 16.4% vs 7.0%. Cytomegalovirus infection or reactivation occurred in 5.5% vs 8.2%.  

The investigators concluded, “Among patients with glucocorticoid-refractory or -dependent chronic GVHD, ruxolitinib led to significantly greater overall response, failure-free survival, and symptom response. The incidence of thrombocytopenia and anemia was greater with ruxolitinib.”

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