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Randomized Controlled Trial
. 2023 Aug 22;7(16):4505-4513.
doi: 10.1182/bloodadvances.2023010310.

Tacrolimus/methotrexate vs tacrolimus/reduced-dose methotrexate/mycophenolate for graft-versus-host disease prevention

Betty K Hamilton  1 , Lisa A Rybicki  2 , Hong Li  2 , Taylor Lucas  1 , Donna Corrigan  1 , Matt Kalaycio  1 , Ronald Sobecks  1 , Rabi Hanna  3 , Seth J Rotz  3 , Robert M Dean  1 , Aaron T Gerds  1 , Deepa Jagadeesh  1 , Claudio Brunstein  1 , Craig S Sauter  1 , Edward A Copelan  4 , Navneet S Majhail  5
Affiliations
Randomized Controlled Trial

Tacrolimus/methotrexate vs tacrolimus/reduced-dose methotrexate/mycophenolate for graft-versus-host disease prevention

Betty K Hamilton et al. Blood Adv. .

Abstract

Tacrolimus (Tac)/methotrexate (MTX) is standard graft-versus-host disease (GVHD) prophylaxis; however, is associated with several toxicities. Tac, reduced-dose MTX (mini-MTX), and mycophenolate mofetil (MMF) have been used but never compared with standard MTX. We performed a randomized trial comparing Tac/MTX (full-MTX) with Tac/mini-MTX/MMF (mini-MTX/MMF) for GVHD prevention after allogeneic hematopoietic cell transplantation (HCT). Patients (pts) receiving first myeloablative HCT using an 8/8 HLA-matched donor were eligible. Primary end points were incidence of acute GVHD (aGVHD), mucositis, and engraftment. Secondary end points included chronic GVHD (cGVHD), organ toxicity, infection, relapse, nonrelapse mortality (NRM), and overall survival (OS). Ninety-six pts were randomly assigned to full-MTX (N = 49) or mini-MTX (N = 47). The majority (86%) used bone marrow grafts. There was no significant difference in grade 2-4 aGVHD (28% mini-MTX/MMF vs 27% full-MTX; P = .41); however higher incidence of grade 3-4 aGVHD (13% vs 4%; P = .07) with mini-MTX/MMF. Pts receiving mini-MTX/MMF had lower grade 3 or 4 mucositis and faster engraftment. There were no differences in moderate-to-severe cGVHD at 1 year or infections. Pts receiving mini-MTX/MMF experienced less nephrotoxicity and respiratory failure. There was no difference in the 1-year relapse (19% vs 21%; P = .89) and OS (72% vs 71%; P = .08), and mini-MTX/MMF was associated with lower but nonsignificant NRM (11% vs 22%; P = .06). Compared with full-MTX, mini-MTX/MMF was associated with no difference in grade 2-4 aGVHD and a more favorable toxicity profile. The higher severe aGVHD warrants further study to optimize this regimen. The trial was registered at www.clinicaltrials.gov as #NCT01951885.

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Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
GVHD outcomes. (A) Cumulative incidence of grade 2 or 4 aGVHD. (B) Cumulative incidence of grade 3 or 4 aGVHD. (C) Cumulative incidence of moderate-to-severe cGVHD.
Figure 2.
Figure 2.
Relapse and survival outcomes. (A) Cumulative incidence of relapse. (B) Cumulative incidence of NRM. (C) OS. (D) GRFS.
See this image and copyright information in PMC

References

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