Ruxolitinib in Patients With Chronic Graft-Versus-Host Disease: 3-Year Final Analysis of Efficacy and Safety From the Phase III REACH3 Study

Introduction: Corticosteroids (CS) are the standard first-line treatment for patients (pts) with chronic graft-versus-host disease (cGvHD), but pts can be unresponsive or become refractory to or dependent on CS (SR/D).Ruxolitinib (RUX), a JAK1/2 inhibitor, is approved for the treatment of pts ≥12 years of age with SR/D-cGVHD, based on the primary outcomes from the randomized, phase III REACH3 (NCT03112603) study, which demonstrated the superior efficacy of RUX vs best available treatment (BAT) in pts with SR/D-cGVHD. Here, we present the final, long-term efficacy and safety outcomes from REACH3. Methods: Pts ≥12 years of age with moderate or severe SR/D-cGVHD were randomized 1:1 to receive either RUX 10 mg twice daily (BID) or investigator-selected BAT and followed for 3 years, till discontinuation or death. The primary analysis was conducted at week 24 (Cycle 7 Day 1 [C7D1]) in randomized pts, then pts entered the extension period (C7-39) in which they continued treatment, switched from BAT to RUX (crossover cohort), or discontinued treatment and entered long-term survival follow-up (FU). Failure-free survival (FFS; key secondary endpoint), duration of response (DOR), overall survival (OS), non-relapse mortality (NRM), malignancy relapse (MR), and safety were analyzed at 3 years (week 156; final data cut off 15 Dec 2022). Overall response rate (ORR) and best overall response (BOR) during the crossover treatment period were analyzed for pts who switched from BAT to RUX on or after C7D1. Results: Of 329 pts randomized, 53 completed the treatment period and 276 discontinued, 115 entered survival FU (RUX: 73/165; BAT:42/164); 70 pts crossed over from BAT to RUX of which 16 completed the crossover treatment period and 24 entered survival FU. Median FFS was longer in the RUX vs BAT arms (38.4 vs 5.7 months; hazard ratio [HR]=0.361, 95% confidence interval [CI]: 0.268, 0.485) with 12-month FFS probabilities of 64.0% (95% CI: 56.1, 70.8) and 28.8% (95% CI: 21.8, 36.1), respectively. Median OS was not reached and there was no difference in risk of death between the arms (HR=0.851, 95% CI: 0.544, 1.331) [Table 1]. Median DOR was 6.4 months (95% CI: 4.9, 11.4) in the BAT arm but was not reached for the RUX arm; notably, the probability of maintaining DOR at 3 years was higher in RUX (59.6%; 95% CI: 50.4, 67.6) vs BAT (26.7%; 95% CI: 18.5, 35.5). NRM event rates were similar between the arms (RUX: 29/165; BAT 34/164), and MR events were similar and low in both arms (