Mini-dose methotrexate combined with methylprednisolone for the initial treatment of acute GVHD: a multicentre, randomized trial
Yu Wang, Qifa Liu, Depei Wu, Zhengli Xu, Ting‐Ting Han, Yuqian Sun, Fen Huang, Zhiping Fan, Na Xu, Feng Chen, Ye Zhao, Yuan Kong, Xiao‐Dong Mo, Lan‐Ping Xu, Xiaohui Zhang, Kai‐Yan Liu, Xiao‐Jun Huang
Abstract
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/m 2 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).