Ruxolitinib for graft-versus-host disease prophylaxis following tacrolimus toxicity: A case series

IntroductionThe data on the safety and feasibility of transitioning from tacrolimus to ruxolitinib for graft-versus-host disease (GVHD) prophylaxis in the early post-allogeneic hematopoietic stem cell transplantation (allo-HCT) period is lacking. Optimal dosing and timing of ruxolitinib remains unclear.Case ReportWe describe four allo-HCT recipients who required early tacrolimus discontinuation due to neurotoxicity (n = 2) or nephrotoxicity (n = 2) and were transitioned to ruxolitinib for GVHD prophylaxis. The patients ranged from 23 to 74 years of age and received reduced-intensity conditioning with standard post-transplant cyclophosphamide-based prophylaxis. Tacrolimus was discontinued between Days +27 and +44.Management and OutcomesRuxolitinib was initiated between Days +29 and +53 at doses ranging between 5 to 15 milligrams per day with the use of a short prednisone bridge in one patient. All four patients experienced resolution of their tacrolimus-related toxicity, and no acute or chronic GVHD events were observed at last follow-up. The primary ruxolitinib-associated adverse event was cytopenia, which was expected. Full or near full chimerism was maintained in all patients.DiscussionThis case series provides early evidence for a safe switch from tacrolimus to ruxolitinib for GVHD prophylaxis in the post-allo-HCT setting with effective GVHD control. Ruxolitinib 5 to 15 milligrams per day appear reasonable when tacrolimus discontinuation is necessary. Prospective studies are needed to define optimal dosing and transition strategies.