Broers Annoek E C, Meijer Ellen, van der Holt Bronno, de Jong Cornelis N, Nur Erfan, van Sluis Geerte L, Choi Goda, van Gelder Michel, Maertens Johan A, Kuball Jürgen, Deeren Dries, Visser-Wisselaar Heleen A, Meulendijks Lamberdina A H M, Cornelissen Jan J
Department of Hematology Erasmus MC Cancer Institute Rotterdam The Netherlands.
Department of Hematology Amsterdam UMC location VU Amsterdam The Netherlands.
Hemasphere. 2024 Dec 11;8(12):e70040. doi: 10.1002/hem3.70040. eCollection 2024 Dec.
Cyclosporine A combined with mycophenolate mofetil (CsA/MMF) has become an established regimen for the prevention of graft-versus-host disease (GVHD) following non-myeloablative (NMA) allogeneic hematopoietic stem cell transplantation (alloHSCT). However, the optimal duration of immunosuppression (IS) has not yet been defined and overtreatment is of concern. We hypothesized that time-restricted IS with CsA/MMF would increase the proportion of patients with non-severe GVHD compared to standard-duration IS, thereby resulting in reduction of the relapse rate and improvement of progression-free survival (PFS) and overall survival (OS). In a prospective randomized, multicenter, phase III trial, patients were allocated (1:1) to standard or time-restricted IS. A total of 389 patients were randomized, of whom 369 were transplanted (184 vs. 185 patients). The primary endpoint, the proportion of patients with non-severe GVHD defined as acute GVHD grades I-II without gut involvement or chronic GVHD not requiring systemic treatment within 180 days posttransplant, was 23% after standard-duration IS versus 24% after time-restricted IS (odds ratio: 1.02; 95% confidence interval (CI) 0.63-1.66, = 0.92). The cumulative incidence of grade III-IV acute GVHD at 6 months posttransplant was not significantly different (14% vs. 18%; = 0.20). The two-year cumulative incidence of chronic extensive GVHD was 50% versus 46% ( = 0.62). There were no significant differences in the rates of relapse/progression, non-relapse mortality, PFS, OS, and GVHD-free, relapse-free survival. Time-restricted IS with CsA/MMF did not increase the proportion of patients with non-severe GVHD, and secondary outcomes were not different compared to standard-duration IS following NMA-matched alloHSCT.
环孢素A联合霉酚酸酯（CsA/MMF）已成为非清髓性（NMA）异基因造血干细胞移植（alloHSCT）后预防移植物抗宿主病（GVHD）的既定方案。然而，免疫抑制（IS）的最佳持续时间尚未确定，过度治疗令人担忧。我们假设，与标准持续时间的IS相比，采用CsA/MMF进行限时IS会增加非重度GVHD患者的比例，从而降低复发率，改善无进展生存期（PFS）和总生存期（OS）。在一项前瞻性随机、多中心III期试验中，患者被（1:1）分配至标准或限时IS组。共有389例患者被随机分组，其中369例接受了移植（184例对185例）。主要终点为移植后180天内非重度GVHD患者的比例，定义为无肠道受累的急性GVHD I-II级或无需全身治疗的慢性GVHD，标准持续时间IS组为23%，限时IS组为24%（优势比：1.02；95%置信区间（CI）0.63-1.66，P = 0.92）。移植后6个月III-IV级急性GVHD累积发生率无显著差异（14%对18%；P = 0.20）。慢性广泛性GVHD的两年累积发生率分别为50%和46%（P = 0.62）。复发/进展率、非复发死亡率、PFS、OS以及无GVHD、无复发生存率均无显著差异。采用CsA/MMF进行限时IS并未增加非重度GVHD患者的比例，与NMA匹配的alloHSCT后标准持续时间的IS相比，次要结局也无差异。
