Improved Efficacy Outcomes With Ruxolitinib for GVHD After Allogeneic Transplantation

Ruxolitinib significantly improved efficacy outcomes over common therapy options for glucocorticoid-refractory acute graft-versus-host disease (GVHD) after allogeneic stem cell transplantation, according to results from a phase 3 trial (N Engl J Med. 2020 Apr 22. Epub ahead of print).

“Acute… [GVHD] remains a major limitation of allogeneic stem-cell transplantation; not all patients have a response to standard glucocorticoid treatment,” explained Robert Zeiser, MD, Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Germany, and colleagues.

Ruxolitinib, a selective Janus kinase inhibitor, showed potential efficacy for glucocorticoid-refractory acute GVHD in a phase 2 trial. This lead Dr Zeiser and colleagues to conduct a phase 3 trial comparing the efficacy and safety of ruxolitinib versus investigator’s choice of therapy (control) for glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation.

The multicenter, open-label, phase 3 trial randomized 309 patients in a 1:1 ratio to receive ruxolitinib (n = 154) or investigator’s choice of therapy from a list of 9 available options (n = 155).

The primary end point was overall response at day 28 and the secondary end point was durable overall response at day 56.

The overall response at day 28 was 62% (96 patients) in the ruxolitinib group compared to 39% (61 patients) in the control group (odds ratio [OR], 2.64; 95% confidence interval [CI], 1.65-4.22; P < 0.001). Additionally, the durable overall response at day 56 was 40% (61 patients) in the ruxolitinib group versus 22% (34 patients) in the control group (OR, 2.38; 95% CI, 1.43-3.94; P < 0.001).

Dr Zeiser and colleagues noted that the estimated cumulative incidence of loss of response at 6 months was lower in the ruxolitinib group (10%) compared to the control group (39%). The median failure-free survival was 5 months with ruxolitinib versus 1 month with the control (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% CI, 0.35-0.60).

Additionally, the median overall survival was 11.1 months versus 6.5 months in the ruxolitinib and control groups, respectively (HR for death, 0.83; 95% CI, 0.60-1.15).

The most commonly reported adverse events up to day 28 were thrombocytopenia (50 [33%] patients in the ruxolitinib group and 27 [18%] patients in the control group), anemia (46 [30%] and 42 [28%], respectively), and cytomegalovirus infection (39 [26%] and 31 [21%], respectively).

“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,” Dr Zeiser and colleagues concluded.—Janelle Bradley