Sirolimus and Mycophenolate Mofetil as Calcineurin Inhibitor-Free Graft-versus-Host Disease Prophylaxis for Reduced-Intensity Conditioning Umbilical Cord Blood Transplantation

The use of calcineurin inhibitors (CNIs) to reduce the risk of graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) requires intensive post-transplantation toxicity monitoring. Sirolimus-based GVHD prophylaxis is associated with a favorable toxicity profile and requires less intensive monitoring. However, the efficacy of sirolimus-based regimen compared with CNI-based regimen has not been evaluated in the setting of reduced-intensity conditioning (RIC) double umbilical cord blood (UCB) HCT. We compared outcomes of patients receiving sirolimus/mycophenolate mofetil (MMF) (n = 37) or cyclosporine (CSA)/MMF (n = 123) in an ongoing phase II study of RIC UCB transplantation. In multiple regression analysis, sirolimus/MMF did not influence the risk of grades II to IV or grades III and IV acute GVHD. In addition, there was no association between type of GVHD prophylaxis and hematopoietic engraftment. Infection density analysis found a significantly lower risk of infections with sirolimus/MMF between days +46 and +180 after HCT compared with CSA/MMF (3.4 versus 6.3 per 1000 patient-days, P =.03); however, no difference was observed before day +45. Sirolimus/MMF use resulted in no thrombotic microangiopathy, fewer instances of elevated serum creatinine >2 mg/dL (14% versus 45%; P < .01), and similar rates of sinusoidal obstruction syndrome (2.7% versus 4%; P = .68), compared with CSA/MMF. Disease-free survival at 1 year was 51% for sirolimus/MMF and 41% for CSA/MMF (P = 41), and sirolimus/MMF use did not influence the risk of nonrelapse mortality or survival. In conclusion, sirolimus/MMF GVHD prophylaxis was better tolerated and resulted in similar rates of GVHD and survival as compared to CSA/MMF after RIC double UCB transplantation. (C) 2016 American Society for Blood and Marrow Transplantation.