文章：

联合细胞因子阻断疗法（CCBT）应用巴利昔单抗与英夫利昔单抗治疗类固醇难治性移植物抗宿主病（SR-GvHD）

Combined Cytokine Blockade Therapy (CCBT) Using Basiliximab and Infliximab for Treatment of Steroid-Refractory Graft-Versus-Host Disease (SR-GvHD)

原文发布日期：22 November 2024

DOI: 10.3390/cancers16233912

类型: Article

开放获取: 是

英文摘要：

Background: The standard first-line treatment for acute graft-versus-host disease (aGvHD) is systemic, high-dose glucocorticoids which have historically had limited responses. Combined cytokine blockade therapy (CCBT) with the monoclonal antibodies infliximab (a TNF-α inhibitor) and basiliximab (an IL-2 receptor blocker) has had limited discussion in the literature. Methods: Sixty patients with steroid-refractory aGVHD were analyzed. The primary objective was to determine the overall response rate (ORR) for CCBT. Secondary outcomes included non-relapse mortality (NRM) and overall survival (OS). Results: ORR for CCBT at day 7, 14, and 28 were 28.3% (17/60; CR 5.0%/PR 23%), 38.3% (23/60; CR 11.3%/PR 27%), and 38.3% (23/60; CR 23.3%/PR 15%), respectively. Patients who received ruxolitinib prior to CCBT had lower ORR (25% CR = 15%/PR = 10%) compared to those who did not (47.5% CR = 27.5%/PR = 20%). In patients with and without ruxolitinib initiated prior to CCBT, NRM at 6 months was 60% (95% CI, 34.5–78) and 47.5% (95% CI, 31–62), while OS at 12 months was 30% (95% CI, 12–50) vs. 40% (95% CI, 25–55), respectively. Conclusions: CCBT has shown potential efficacy in steroid-refractory GI aGvHD, and given the observed ORR when used as second-line therapy, CCBT could serve as an acceptable alternative for patients who are ruxolitinib-intolerant. Ruxolitinib-refractory GI GvHD remains an area of unmet need and CCBT can provide salvage therapy for some patients.

摘要翻译： 

背景：急性移植物抗宿主病（aGvHD）的标准一线治疗为全身性大剂量糖皮质激素，但该疗法历史应答率有限。联合细胞因子阻断疗法（CCBT）采用单克隆抗体英夫利西单抗（TNF-α抑制剂）与巴利昔单抗（IL-2受体阻断剂），目前文献中相关讨论较少。方法：本研究纳入60例类固醇难治性aGVHD患者。主要研究终点为评估CCBT的总体应答率（ORR），次要终点包括非复发死亡率（NRM）与总生存期（OS）。结果：CCBT在第7、14、28天的ORR分别为28.3%（17/60；完全缓解率5.0%/部分缓解率23%）、38.3%（23/60；完全缓解率11.3%/部分缓解率27%）及38.3%（23/60；完全缓解率23.3%/部分缓解率15%）。与未接受芦可替尼治疗的患者（ORR 47.5%，完全缓解率27.5%/部分缓解率20%）相比，CCBT前使用芦可替尼治疗者的ORR较低（25%，完全缓解率15%/部分缓解率10%）。在CCBT前是否使用芦可替尼的两组患者中，6个月NRM分别为60%（95% CI，34.5–78）与47.5%（95% CI，31–62），12个月OS分别为30%（95% CI，12–50）与40%（95% CI，25–55）。结论：CCBT在类固醇难治性胃肠道aGvHD中显示出潜在疗效，其作为二线疗法观察到的ORR提示，对于芦可替尼不耐受患者，CCBT可作为可行的替代方案。芦可替尼难治性胃肠道GvHD仍是未满足的临床需求领域，CCBT可为部分患者提供挽救治疗选择。

原文链接：

Combined Cytokine Blockade Therapy (CCBT) Using Basiliximab and Infliximab for Treatment of Steroid-Refractory Graft-Versus-Host Disease (SR-GvHD)