Transitioning tacrolimus to sirolimus in allogeneic hematopoietic cell transplantation

Objectives: Calcineurin inhibitor (CNI) use for acute graft-versus-host disease (aGVHD) prophylaxis in allogeneic hematopoietic cell transplantation (allo-HCT) recipients has been associated with toxicities. Toxicities may be managed by converting CNI to sirolimus as often done in solid organ transplantation. This study aimed to characterize allo-HCT patients who completely transitioned from tacrolimus to sirolimus and evaluate the incidence of aGVHD within 100 days post-transition, overall survival (OS), and incidence of relapse. Methods: Safety and efficacy data were collected at baseline and at day 30 and 90 post-transition from tacrolimus to sirolimus and at one-year post-HCT. Results: Most patients who transitioned had acute leukemia, received a matched unrelated donor allo-HCT, and transitioned due to nephrotoxicity or neurotoxicity. The resolution rate was 83% and 48% in the nephrotoxicity group, 78% and 61% in the neurotoxicity group, 33% and 33% in the group that developed both nephrotoxicity and transplant-associated thrombotic microangiopathy at 30 and 90 days of assessments, respectively. Patients who transitioned before day 55 post-allo-HCT were more likely to develop new or worsening aGVHD. The one-year OS and relapse rates were 37% and 20%, respectively. Conclusions: The conversion from tacrolimus to sirolimus demonstrates promising resolution of acute toxicities; however, overall mortality remains high.