Impact of Concomitant Azoles on Ruxolitinib Treatment in Patients With GVHD: Post Hoc Analyses of REACH2 and REACH3.

Azole antifungal agents, commonly used for preventing invasive fungal infections in graft-versus-host disease (GVHD), are known to affect ruxolitinib metabolism. Post hoc analyses of the REACH2/REACH3 phase 3 trials (ClinicalTrials.gov: NCT02913261/NCT03112603) examined the impact of these clinically relevant drug interactions on ruxolitinib treatment outcomes in patients with steroid-refractory acute GVHD (aGVHD; REACH2) and steroid-refractory/steroid-dependent chronic GVHD (cGVHD; REACH3). In REACH2, the overall response rate (ORR) at Day 28 was significantly higher with ruxolitinib versus best available therapy (BAT; 67.5% vs 44.3%; P=0.0003) among patients who received concomitant azoles; among those who did not, Day 28 ORR was 45.9% vs 28.6%, respectively. In REACH3, ORR at Week 24 was significantly higher with ruxolitinib versus BAT in patients who did (46.6% vs 29.4%; P=0.006) or did not receive (57.1% vs 19.4%; P<0.0001) concomitant azoles. Concomitant azoles neither increased the rate of cytopenias in patients treated with ruxolitinib in REACH2/REACH3, nor impacted the median (range) dose of ruxolitinib up to Day 28 in REACH2 (azoles/no azoles, 20.0 [9.0-21.0]/20.0 [8.4-20.0] mg/day) or Week 24 in REACH3 (azoles/no azoles, 19.4 [4.8-20.5]/19.9 [5.5-20.0] mg/day). However, patients receiving concomitant azoles were more likely to have ruxolitinib dose modifications in REACH2/REACH3, highlighting the importance of dose optimization in these patients. Overall, concomitant azole treatment was generally well tolerated and did not affect treatment outcomes with appropriate ruxolitinib dose optimization. Consistent with primary REACH2/REACH3 results, ruxolitinib provided greater clinical benefit than BAT in patients with steroid-refractory aGVHD and steroid-refractory/steroid-dependent cGVHD, irrespective of concomitant azole treatment.