Effects of Concomitant Azoles on Ruxolitinib Treatment in Patients with Chronic Graft-Versus-Host Disease: A Post Hoc Analysis from the Randomized Phase 3 REACH3 Study

Introduction Ruxolitinib (RUX) is an oral, selective Janus kinase (JAK)1/JAK2 inhibitor approved for steroid-refractory chronic graft-versus-host disease (SR-cGVHD) in patients (pts) aged ≥12 years after failure of 1 or 2 lines of systemic therapy. The open-label phase 3 REACH3 trial demonstrated higher response rates with RUX 10 mg twice daily vs best available therapy (BAT) and allowed for steroid tapering in pts with moderate or severe SR or steroid-dependent (SD) cGVHD. Antifungal prophylaxis with azoles is common in pts with cGVHD, however, there is potential for drug-drug interactions with RUX that may lead to drug accumulation impacting RUX safety and efficacy. Objective Describe the impact of concomitant azoles on outcomes in pts with cGVHD treated with RUX or BAT in REACH3. Methods This post hoc analysis examined overall response rate (ORR [complete response + partial response]) at Week (Wk) 24 and best overall response (BOR) at any time for RUX and BAT treatment in pts who received or did not receive concomitant azoles including posaconazole, voriconazole, fluconazole, isavuconazole, itraconazole, fosfluconazole, or isavuconazonium sulfate. Odds ratio and 95% CI were calculated using stratified Cochran-Mantel-Haenszel test. Results Of the 165 pts who received RUX in REACH3, 116 (70.3%) received concomitant azoles and 49 (29.7%) did not. Of 164 pts who received BAT in REACH3, 102 (62.2%) received concomitant azoles and 62 (37.8%) did not. Pt demographics, clinical characteristics, and RUX treatment patterns are shown in Table 1.RUX had greater ORR than BAT at Wk 24 for pts who did or did not receive azoles (Figure 1A). BOR was numerically higher with RUX vs BAT for pts who received azoles (Figure 1B). Similar ORR and BOR were noted between RUX pts receiving and not receiving concomitant azoles. Conclusions Concomitant treatment with azoles does not impact RUX outcomes, and RUX provides greater clinical benefit than BAT for pts with SD- or SR-cGVHD. Impact of azoles on development of cytopenias will be included at presentation. RUX prescribing information should be followed for empiric dose adjustment in pts on concomitant azoles.