Assessing PTCy–Ruxolitinib as an Alternative to Calcineurin-Based GVHD Prevention
Moiseev I, Drokov M, Kitaeva Y, et al. A Randomized, Multicenter Phase II Trial to Compare Prophylaxis of Graft Versus Host Disease With Tacrolimus and Mycophenolate Mofetil Versus Ruxolitinib After Post-Transplant Cyclophosphamide. Transplantation and Cellular Therapy. 2026; (doi:10.1016/j.jtct.2026.04.042).
Post-transplantation cyclophosphamide (PTCy) is gaining traction as standard prevention against graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (HCT), but more insight is needed to refine the approach. While PTCy is most often used in combination with the immunosuppressive agents tacrolimus (Tac) and mycophenolate mofetil (MMF), new research suggests that pairing PTCy with oral ruxolitinib (PTCy-Ruxo) may be as effective but even safer. The Phase II study involved 128 adults with acute myeloid leukemia and acute lymphoblastic leukemia in complete remission. Half received PTCy-Ruxo, and half received PTCy-Tac-MMF. At 125-day follow-up, the cumulative incidence of acute GVHD grade II-IV was 12.9% in the PTCy-Ruxo group compared with 21.2% in the PTCy-Tac-MMF group. The cumulative incidence of moderate and severe chronic GVHD in the two groups was 24.2% and 39.5%, respectively. PTCy-Ruxo was also associated with a lower rate of grade 2-4 renal injury, endothelial complications, and severe poor graft function. Based on noninferior efficacy compared with PTCy-Tac-MMF and better safety performance, the investigators recommend further exploration of PTCy-Ruxo as an alternative to calcineurin-based prophylaxis protocols.