Presenting Authors: Mary C. Cash, PharmD, BCOP, and Erin M. Eberwein, PharmD, BCOP, Duke University Hospital, Durham, NC
Co-Authors: Elizabeth R. Eubanks, PharmD, MPH, BCPS, BCOP, and Daniel Schrum, PharmD, BCOP, Duke University Hospital, Durham, NC; Joshua Burrows, MS, and Hui-Jie Lee, PhD, Duke University School of Medicine, Department of Biostatistics and Bioinformatics, Durham, NC
BACKGROUND: The use of post-transplant cyclophosphamide, tacrolimus, and mycophenolate (PTCy-Tac-MMF) has gained popularity for the prevention of graft-versus-host disease (GVHD) following hematopoietic stem cell transplant (HSCT) with an HLA-matched related donor (MRD) or an HLA-matched unrelated donor (MUD) donor. Although the results of BMT-CTN 1703 solidified the role of PTCy-Tac-MMF as standard of care following reduced-intensity conditioning, limited data exist evaluating its use following myeloablative conditioning.
OBJECTIVE: The purpose of this study is to compare the efficacy and safety of PTCy-Tac-MMF and tacrolimus and methotrexate (Tac-MTX) as GVHD prevention among patients who underwent HSCT from a MRD or MUD following myeloablative conditioning.
METHODS: This single center, retrospective cohort study included patients who received an HSCT from an MRD or MUD following myeloablative conditioning from January 2019 to August 2022. The primary outcome, 1-year GVHD-free, relapse-free survival (GRFS), was estimated by Kaplan Meier method and compared between the groups using a log-rank test. The secondary outcomes included the incidence of GVHD, time to engraftment, time of relapse, overall survival (OS), and incidence of adverse events.
RESULTS: The study included 90 patients, of whom 77 (85.6%) received Tac-MTX and 13 (14.4%) received PTCy-Tac-MMF. The 1-year GRFS rate was 21% (95% confidence interval [CI], 0%-44%) for PTCy-Tac-MMF and 6.5% (95% CI, 1%-12%) for Tac-MTX (P=.066). The rate of acute GVHD (aGVHD) was 30.8% versus 68.8%, and the rate of chronic GVHD (cGVHD) was 38.5% versus 54.5% in the PTCy-Tac-MMF and Tac-MTX groups, respectively. Grade 3 or 4 aGVHD and moderate-to-severe cGVHD were less frequent among those who received PTCy-Tac-MMF. Neutrophil engraftment was achieved in 92.3% of those receiving PTCy-Tac-MMF (median time to engraftment, 17.5 days; interquartile range [IQR], 15.8-20.2) compared with 97.4% of those receiving Tac-MTX (median, 18 days; IQR, 16-20). The 1-year cumulative incidence of relapse was 15% (95% CI, 2.2%-40%) and 13% (95% CI, 6.6%-22%) for PTCy-Tac-MMF and Tac-MTX, respectively. The 1-year OS was 68% (95% CI, 43%-94%) among those receiving PTCy-Tac-MTX and 70% (95% CI, 60%-80%) among those receiving Tac-MTX.
CONCLUSION: Tac-MTX did not have statistically different 1-year GRFS versus PTCy-Tac-MMF. Lower rates of GVHD, including grade 3 or 4 aGVHD and moderate-to-severe cGVHD, were observed among the PTCy-Tac-MMF cohort. The 1-year relapse rates and 1-year OS were similar between the 2 groups. Limitations include the small sample size of the PTCy-Tac-MMF cohort and a short time of follow-up. Future directions include extending the study time period to include additional patients in the PTCy-Tac-MMF cohort and adjusting for prognostic factors.
- Bolaños-Meade J, Hamadani M, Wu J, et al. Post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis. N Engl J Med. 2023;388:2338-2348.