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期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-03016-4

摘要内容如下：

下消化道急性移植物抗宿主病（aGVHD）是异基因造血干细胞移植（allo-HSCT）患者发病和死亡的主要原因。Vedolizumab是一种肠道选择性抗α4β7整合素单克隆抗体，通过抑制Gi归巢T淋巴细胞的迁移来减少肠道炎症。在一项随机、双盲、安慰剂对照的3期临床试验中，评估了在标准移植物抗宿主病（GVHD）预防（钙调神经磷酸酶抑制剂联合甲氨蝶呤/霉酚酸酯）中加入vedolizumab预防无关供体allo-HSCT后低GI aGVHD的有效性和安全性。在COVID-19大流行期间，343名患者被随机分组（n=174例vedolizumab，n=169例安慰剂），333名患者接受≥1次静脉注射300mg vedolizumab（n=168）或安慰剂（n=165），并接受allo-HSCT。达到主要终点；Kaplan-Meier（95%可信区间）估计的allo-HSCT后+180天的低GI无aGVHD生存率，vedolizumab组为85.5%（79.2-90.1），安慰剂组为70.9%（63.2-77.2）（风险比为0.45；95%可信区间为0.27-0.73；P<0.001）。对于allo-HSCT后+180天分析的5个关键次要疗效终点，与安慰剂相比，vedolizumab的低GI无aGVHD生存率和无复发生存率以及C-D级无aGVHD生存率显著更高。在其他关键的次要终点（无复发死亡率、总生存率和B-D级无aGVHD生存率）方面，分别没有发现显著的治疗差异。在接受≥1剂研究治疗的患者（n=334）中分析的治疗相关严重不良事件发生率为6.5%（n=11/169）vedolizumab vs.8.5%（n=14/165）安慰剂。当加入基于钙调磷酸酶抑制剂的标准GVHD预防时，与安慰剂相比，vedolizumab的低GI无aGVHD存活率显著更高。ClinicalTrials.gov标识符：NCT03657160。

英文原文如下：

Abstracts

Acute graft-versus-host disease (aGVHD) of the lower gastrointestinal (GI) tract is a major cause of morbidity and mortality in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). Vedolizumab is a gut-selective anti-α4β7 integrin monoclonal antibody that reduces gut inflammation by inhibiting migration of GI-homing T lymphocytes. The efficacy and safety of vedolizumab added to standard GVHD prophylaxis (calcineurin inhibitor plus methotrexate/mycophenolate mofetil) was evaluated for prevention of lower-GI aGVHD after unrelated donor allo-HSCT in a randomized, double-blind, placebo-controlled phase 3 trial. Enrollment closed early during the COVID-19 pandemic with 343 patients randomized (n = 174 vedolizumab, n = 169 placebo), and 333 received ≥1 intravenous dose of 300 mg vedolizumab (n = 168) or placebo (n = 165) and underwent allo-HSCT. The primary end point was met; Kaplan-Meier (95% confidence interval) estimated rates of lower-GI aGVHD-free survival by day +180 after allo-HSCT were 85.5% (79.2-90.1) with vedolizumab versus 70.9% (63.2-77.2) with placebo (hazard ratio, 0.45; 95% confidence interval, 0.27-0.73; P < 0.001). For the 5 key secondary efficacy end points analyzed by day +180 after allo-HSCT, rates of lower-GI aGVHD-free and relapse-free survival and grade C-D aGVHD-free survival were significantly higher with vedolizumab versus placebo. No significant treatment differences were found for the other key secondary end points of non-relapse mortality, overall survival and grade B-D aGVHD-free survival, respectively. Incidence of treatment-related serious adverse events analyzed in patients receiving ≥1 dose of study treatment (n = 334) was 6.5% (n = 11 of 169) vedolizumab versus 8.5% (n = 14 of 165) placebo. When added to standard calcineurin inhibitor-based GVHD prevention, lower-GI aGVHD-free survival was significantly higher with vedolizumab versus placebo. ClinicalTrials.gov identifier: NCT03657160 .

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