Graft-versus-host disease (GvHD) occurs in ~50% of patients who undergo allogeneic haematopoietic stem cell transplantation and results in considerable morbidity and mortality. In May 2019, the FDA approved the JAK1/2 inhibitor ruxolitinib for patients ≥12 years of age with glucocorticoid-refractory acute GvHD (aGvHD) based on the results of the single-arm phase II REACH1 trial. Now, a year later, data from the phase III REACH2 trial confirm the benefits of ruxolitinib in this setting.

In REACH2, 309 patients were assigned (1:1) to receive ruxolitinib or investigator’s choice of one of nine commonly used treatments for steroid-refractory aGvHD. The objective response rate (ORR) at day 28 was 62% with ruxolitinib versus 39% in the control group (P <0.001), with complete response rates of 34% versus 19%. The percentage difference in ORR between the treatment groups was fairly consistent across aGvHD grades (18–30%) and was greatest for grade IV disease. The durable ORR at day 56 was 40% versus 22% (P <0.001). The proportion of patients with loss of response at 6 months (10% versus 39%), failure-free survival (median 5 months versus 1 month; HR 0.46, 95% CI 0.35–0.60) and overall survival (median 11.1 months versus 6.5 months; HR 0.83, 95% CI 0.60–1.15) also favoured ruxolitinib.

With regard to toxicity, increased day-28 rates of any-grade thrombocytopenia and cytomegalovirus infection with ruxolitinib were the most obvious differences (33% and 26%, respectively, compared with 18% and 21% in the control group). However, more patients in the ruxolitinib group required dose modifications (38% versus 9%) or discontinued treatment (11% versus 5%).

Ruxolitinib is the only new treatment for aGvHD to be approved in the past 30 years, despite trials of numerous agents. REACH2, the first phase III trial demonstrating the superiority of any aGvHD treatment, corroborates the results of REACH1 and the use of ruxolitinib in the ~60% of patients with aGvHD that is unresponsive to steroids.