(064) Effects of Concomitant Azoles on Ruxolitinib Treatment in Patients with Acute Graft-Versus-Host-Disease: A Post Hoc Analysis From the Randomized Phase 3 REACH2 Study

Poster Abstract:

Background: The oral Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib (RUX) is approved for steroid-refractory acute graft-versus-host-disease (SR-aGVHD). The open-label phase 3 REACH2 study demonstrated higher response rates with RUX vs best available therapy (BAT) in pts aged ≥12 y with grade II–IV SR-aGVHD. Antifungal prophylaxis with azoles is common in pts with aGVHD; 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 patients with aGVHD treated with RUX or BAT REACH2.

Methods: This post hoc analysis examined overall response rate (ORR [complete response (CR) + partial response (PR)] at Day 28 (D28) and best overall response (BOR) at any time up to D28 for RUX and BAT treatment in pts who did or did not receive concomitant azoles including posaconazole, voriconazole, fluconazole, isavuconazole, itraconazole, fosfluconazole, or isavuconazonium sulfate. Cytopenias were defined as any platelet count < 30×109 cells/L, hemoglobin < 8 g/dL, white blood cell count < 5×109 cells/L, or absolute neutrophil count < 1×109 cells/L.

Results: Of 154 pts who received RUX in REACH2, 117 (76.0%) received concomitant azoles and 37 (24.0%) did not. Of 155 pts who received BAT in REACH2, 106 (68.4%) received concomitant azoles and 49 (31.6%) did not. Pt demographics and clinical characteristics of pts were similar between groups. RUX treatment patterns will be included at final presentation.
RUX had greater ORR than BAT at D28 for pts who received azoles (67.5% vs 44.3%, respectively). The BOR at D28 in pts who received azoles was 87.2% in the RUX group and 66.0% in the BAT group. A numerically higher rate of ORR and BOR was observed for RUX and BAT pts who received azoles vs no azoles. No differences were observed in the development of cytopenias at D28 for RUX and BAT pts who received azoles vs no azoles.

Conclusion: Concomitant treatment with azoles does not impact outcomes, and RUX provides greater clinical benefit than BAT for pts with SR-aGVHD. REACH2 starting dose of RUX 10 mg BID appears to be well tolerated in most patients with concomitant azoles. RUX prescribing information guidelines should be followed for empiric dose adjustment in patients on concomitant azoles.

References (must also be included in final poster): N/A