BMC Medicine (Apr 2024)

Mini-dose methotrexate combined with methylprednisolone for the initial treatment of acute GVHD: a multicentre, randomized trial

  • Yu Wang,
  • Qi-Fa Liu,
  • De-Pei Wu,
  • Zheng-Li Xu,
  • Ting-Ting Han,
  • Yu-Qian Sun,
  • Fen Huang,
  • Zhi-Ping Fan,
  • Na Xu,
  • Feng Chen,
  • Ye Zhao,
  • Yuan Kong,
  • Xiao-Dong Mo,
  • Lan-Ping Xu,
  • Xiao-Hui Zhang,
  • Kai-Yan Liu,
  • Xiao-Jun Huang

DOI
https://doi.org/10.1186/s12916-024-03395-y
Journal volume & issue
Vol. 22, no. 1
pp. 1 – 12

Abstract

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Abstract Background There is an urgent unmet need for effective initial treatment for acute graft-versus-host disease (aGVHD) adding to the standard first-line therapy with corticosteroids after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Methods We performed a multicentre, open-label, randomized, phase 3 study. Eligible patients (aged 15 years or older, had received allo-HSCT for a haematological malignancy, developed aGVHD, and received no previous therapies for aGVHD) were randomly assigned (1:1) to receive either 5 mg/m2 MTX on Days 1, 3, or 8 and then combined with corticosteroids or corticosteroids alone weekly. Results The primary endpoint was the overall response rate (ORR) on Day 10. A total of 157 patients were randomly assigned to receive either MTX plus corticosteroids (n = 78; MTX group) or corticosteroids alone (n = 79; control group). The Day 10 ORR was 97% for the MTX group and 81% for the control group (p = .005). Among patients with mild aGVHD, the Day 10 ORR was 100% for the MTX group and 86% for the control group (p = .001). The 1-year estimated failure-free survival was 69% for the MTX group and 41% for the control group (p = .002). There were no differences in treatment-related adverse events between the two groups. Conclusions In conclusion, mini-dose MTX combined with corticosteroids can significantly improve the ORR in patients with aGVHD and is well tolerated, although it did not achieve the prespecified 20% improvement with the addition of MTX. Trial registration The trial was registered with clinicaltrials.gov (NCT04960644).

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