Ruxolitinib in Patients With Corticosteroid-Refractory or Corticosteroid-Dependent Chronic Graft-Versus-Host Disease: 3-Year Final Analysis of the Phase III REACH3 Study

Abstract

In REACH3 (ClinicalTrials.gov identifier: NCT03112603), ruxolitinib was investigated versus best available therapy (BAT) for 3 years in patients with steroid-refractory/dependent chronic graft-versus-host-disease (SR/D-cGVHD). Patients received ruxolitinib (10 mg twice daily) or BAT for 24 weeks; thereafter (weeks 24-156), patients continued randomized treatment, entered long-term survival follow-up, or crossed over from BAT to ruxolitinib. In 329 randomly assigned patients (ruxolitinib: 165; BAT: 164), the median failure-free survival (FFS) was 38.4 months for ruxolitinib versus 5.7 months for BAT (hazard ratio, 0.36 [95% CI, 0.27 to 0.49]). Median duration of response (DOR) was not reached for ruxolitinib versus 6.4 months for BAT. Ruxolitinib-treated patients had a higher probability of FFS (ruxolitinib: 56.5%; BAT: 18.2%) and maintaining a response (ruxolitinib: 59.6%; BAT: 26.7%) at 36 months. Median overall survival was not reached. Nonrelapse mortality and malignancy relapse/recurrence events were low. In 70 patients who crossed over to ruxolitinib, the overall response rate (50.0%) at week 24 and best overall response (81.4%) during the crossover period were consistent with the primary analysis of randomly assigned patients. No new safety signals were observed. Ruxolitinib provided longer FFS and DOR than BAT, demonstrating sustained efficacy and manageable safety over 3 years of follow-up in patients with SR/D-cGVHD.

FIG 1.

Kaplan-Meier analysis of (A) FFS and (B) DOR in the full analysis set. FFS is a composite end point that includes relapse/recurrence of underlying disease or death due to underlying disease, nonrelapse mortality, or addition/initiation of another systemic therapy for cGVHD. DOR is defined as the first response until progression, death, or the date of additional systemic therapies. BAT, best available therapy; cGVHD, chronic graft-versus-host disease; DOR; duration of response; FFS, failure-free survival; HR, hazard ratio; NE, not estimable (not reached).

FIG 2.

(A) ORR at week 24 and (B) BOR up to week 24 of the crossover period in the crossover population and in the primary analysis population at week 24 of the primary treatment period for REACH3. ^aORR was the primary end point and BOR was a key secondary end point in the primary analysis of the REACH3 at week 24. BAT, best available therapy; BOR, best overall response; CR, complete response; ORR, overall response rate; PR, partial response.