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Sirolimus is an acceptable alternative to tacrolimus for graft-versus-host disease prophylaxis after haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide
Elmariah, H., Otoukesh, S., Kumar, A., Ali, H., Arslan, S., Shouse, G., Pourhassan, H., Nishihori, T., Faramand, R., Mishra, A., et al
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND Graft-versus-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy), tacrolimus (TAC) and mycophenolate mofetil (MMF) for allogeneic haploidentical donor (haplo) hematopoietic cell transplantation (HCT) results in comparable outcomes to matched unrelated donor transplantation. A phase II study from Moffitt Cancer Center substituting sirolimus (SIRO) in place of TAC reported comparable rates of grade II-IV acute GVHD. Many centers have substituted SIRO for TAC in this setting based on a preferred side effect profile, though comparative data is limited. OBJECTIVE The objective of this study is to compare outcomes of haplo HCT with PTCy/SIRO/MMF versus PTCy/TAC/MMF. STUDY DESIGN We retrospectively compared haplo HCT outcomes with PTCy/SIRO/MMF versus PTCy/TAC/MMF. Included were all consecutive patients receiving haplo donor T cell replete peripheral blood stem cell graft HCT for hematologic malignancies at Moffitt Cancer Center or the City of Hope National Medical Center between 2014 and 2019. RESULTS A total of 423 patients were included, of which 84 (20%) received SIRO and 339 (80%) received TAC. Median age for all patients was 54 (range 18 to 78) years, and median follow-up for entire study cohort was 30 months. SIRO group had a higher proportion of patients ≥60 years (58% versus 34%, P = <.01), and the groups also differed in diagnosis type, conditioning regimen, and cytomegalovirus serostatus. There were no significant differences in the rates of grade II-IV acute GVHD (45% versus 47%, P = .6) at day +100 or chronic GVHD (47% versus 54%, P = .79) at 2 years post-HCT. In multivariate analysis, neutrophil engraftment at day +30 was significantly better with TAC (OR = 0.30, CI 0.1 to 0.83, P = .02) with a median time to engraftment of 17 days versus 18 days for SIRO, but platelet engraftment was similar in both groups. Otherwise, in multivariate analysis, GVHD prophylaxis type had no significant influence on acute or chronic GVHD, nonrelapse mortality, relapse, GVHD-free relapse-free survival, disease free survival, or overall survival after peripheral blood haplo HCT. CONCLUSIONS These findings suggest that SIRO is a comparable alternative to TAC in combination with PTCy/MMF for GVHD prophylaxis, resulting in overall similar clinical outcomes despite delay in engraftment after peripheral blood haplo HCT. While TAC remains the standard of care, SIRO may be substituted based on the side effect profile of these medications with consideration of patient medical comorbidities at HCT.