Humanized Anti-CD25 Monoclonal Antibody Replacing MTX for Graft-Versus-Host Disease Prophylaxis in Haploidentical Hematopoietic Stem Cell Transplantation

Abstract

Introduction Currently, a short course of methotrexate (MTX) remains the classical regimen for the prevention of graft-versus-host disease (GVHD) in haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Although MTX was widely applied for GVHD prophylaxis, it has been reported to be associated with significant toxicity and considerable side effects. We conducted a prospective, single-center, non-randomized controlled study to evaluate whether MTX can be safely removed from GVHD prophylaxis regimen after transplantation. Methods We prospectively reported and analyzed the data of 149 patients with hematologic malignancies who received haplo-HSCT from May 2022 to January 2023, and followed up until July 10, 2023. Patients were voluntarily enrolled in two groups according to different prevention programs of GVHD. A total of 82 patients were administrated with a combination of cyclosporine (CsA) or tacrolimus, mycophenolate mofetil (MMF), anti-human thymocyte immunoglobulin (ATG), MTX (15mg, +1d, 10mg, +3d, 10mg, +6d), and humanized anti-CD25 monoclonal antibody (Xenopax, 25mg, +0d, +4d) (single-dose anti-CD25 with MTX group). A total of 67 patients were given with CsA or tacrolimus, MMF, ATG and humanized anti-CD25 monoclonal antibody (Xenopax, 50mg, +0d, +4d) (double-dose anti-CD25 group). This study is registered with the Chinese Clinical Trial Registry (chictr.org.cn: ChiCTR2200060184). Results Compared with the single-dose anti-CD25 with MTX group, the median time to achieve neutrophil and platelet engraftment was shorten in double-dose anti-CD25 group (neutrophil: 9 days (7-20) vs 11 days (7-39), P=0.000; platelet: 9 days (7-30) vs 11 days (7-46), P=0.001). The incidence of total oral mucositis (OM) and grade 2-4 OM were significantly reduced in double-dose anti-CD25 group (total OM: 40.29% vs 63.41%, P=0.003; grade 2-4: 7.46% vs 32.05%, P=0.000). The median duration of OM was remarkably shorter in double-dose anti-CD25 group (5 days (2-18) vs 11 days (3-30), P=0.000). Lower cumulative incidence (CI) of grade II-IV aGVHD was observed in double-dose anti-CD25 group than in single-dose CD25 with MTX group (16.7 ± 4.6% vs 28.4 ± 5.0%, P=0.063). There was no statistical difference in two groups of the 100-day CI of grade III-IV aGVHD (6.1 ± 3.0% vs 13.6 ± 3.8%, P=0.123). Lower CI of cGVHD were occurred in double-dose anti-CD25 group (8.4 ± 4.1% vs 20.3 ± 5.1%, P=0.073). The CI of GVHD/relapse-free survival in double-dose anti-CD25 group was remarkably improved than that in single-dose CD25 with MTX group (73.9 ± 5.5% vs 55.6 ± 5.7%, P=0.044). No significant difference occurred in two groups of the overall CIs of CMV viremia, EBV viremia, overall survival, disease-free survival, relapse and treatment-related mortality. Conclusions Based on the efficacy and safety of the clinical trial results at our transplant center, replacing MTX with a single dose of humanized anti-CD25 monoclonal antibody is a promising GVHD prophylaxis for haplo-HSCT.