Ruxolitinib Tops Best Therapy in Steroid-Refractory cGVHD

Ruxolitinib treatment has resulted in durable clinical benefit among patients with steroid-refractory/dependent chronic graft-versus-host disease (GVHD) treated in the phase III REACH3 study. In comparison with best available therapy (BAT), a favorable benefit/risk ratio was observed with ruxolitinib in this study.¹

“About half of [the] people developing chronic GVHD have steroid-refractory/steroid-dependent disease. We know that this challenging population often receives multiple other lines of therapy and requires years of treatment. REACH3 showed that ruxolitinib treatment results in high response rates that are frequently durable,” Stephanie Lee, MD, MPH, a hematologist and blood and marrow transplant physician-scientist serving as professor and associate director in the Clinical Research Division at Fred Hutch Cancer Center told Blood Cancers Today.

REACH3 randomly assigned 329 patients with chronic GVHD to receive either ruxolitinib 10 mg (n =165) or BAT (n = 164). Patients were followed for a median of 73.1 months (1.9-1690 months) in the ruxolitinib arm and 26.1 months (1.0-171.6 months) in the BAT arm.

Patients treated with ruxolitinib had a median failure-free survival (FFS) of 38.4 months compared with only 5.4 months with BAT (Hazard ratio [HR], 0.36; 95% CI, 0.27-0.49). No difference in risk for death was observed between the two treatment arms (HR, 0.85; 95% CI, 0.54-1.33).

The median duration of response (DOR) was not reached for ruxolitinib versus 6.4 months (95% CI, 4.9-11.4 months) for the BAT arm, and patients who received ruxolitinib were more likely to sustain a response up to 36 months. Notably, 3 of the 21 patients who tapered off ruxolitinib experienced disease recurrence.

“This study allowed crossover from the BAT to the ruxolitinib arm. It looks like [the] results after crossover were similar between patients originally assigned to ruxolitinib and those who received it after first getting BAT, explained Dr. Lee. “The study wasn’t designed to look at what happens after ruxolitinib was tapered off after patients responded, but it is reassuring that chronic GVHD recurrence rates were <15%,” she added.

Patients included in the crossover analysis set had an overall response rate of 50.0 (95%CI, 37.8%-62.2%) and a best overall response of 81.4% (95% CI, 70.3%-89.7%).

“With much longer follow-up, no new safety signals were seen. This is important because people with chronic GVHD require prolonged treatment so, it is critical that any agent used for chronic GVHD is safe and tolerable with extended administration.”

To date, there is an unmet need for new options beyond corticosteroids, according to Dr. Lee and colleagues. Considering that ruxolitinib is already an FDA-approved option for chronic GVHD in later-line settings, ruxolitinib may one day be an option in the first-line.