体外光分离术与全身性免疫抑制治疗免疫相关不良事件的比较：一项前瞻性双臂研究的中期分析。
Extracorporeal photopheresis vs. systemic immunosuppression for immune-related adverse events: Interim analysis of a prospective two-arm study.
机构信息
Department of Dermatology and Allergy, LMU University Hospital, LMU Munich, Munich, Germany; SERIO-Registry (www.serio-registry.org).
Division of Clinical Pharmacology, Klinikum der Universität München, Munich, Germany.
出版信息
Eur J Cancer. 2024 Nov;212:115049. doi: 10.1016/j.ejca.2024.115049. Epub 2024 Sep 27.
BACKGROUND
Checkpoint inhibitor-induced steroid-refractory (sr) and steroid-dependent (sd) immune-related adverse events (irAE) account for about 11 % of irAE. Although these patients face worse outcomes due to irAE mortality and/or sustained immunosuppression, which impairs anti-tumor response, there is no established second-line treatment based on prospective trial data.
METHODS
This prospective comparative study investigates outcomes of extracorporeal photopheresis (ECP), an immunomodulating therapy, versus second-line immunosuppressants (SLI) in sr/sd-irAE. The primary endpoint was longitudinal change in immunophenotype; secondary endpoints were outcome of irAE and tumor response. Patient demographics, quality of life (EORTC QLQ-C30; global health status (GHS/QoL)) and longitudinal blood samples were analyzed at baseline; in weeks 1, 4, 8, and 12.
RESULTS
At interim analysis, 21 patients (11 ECP, 10 SLI) with 7 different sr/sd-irAE were included. Compared with the SLI group, the ECP group demonstrated a higher clinical response rate of irAE (93 % vs. 80 %; 95 % CI 0.83-1.92; P = 0.54) and a better GHS/QoL score throughout all follow-up visits. ECP patients showed a numerically higher overall survival (23 vs. 12 months; 95 % CI 0.02-3.02; P = 0.27) and lower cancer progression rates (33 % vs. 67 %; 95 % CI 0.09-1.60; P = 0.52). Immunophenotyping revealed changes in immune cell populations and the regulation of immune checkpoints. There were no significant safety issues in either treatment group.
CONCLUSION
This prospective comparative study supports the clinical efficacy of ECP in the treatment of sr/sd-irAE in comparison to the SLI cohort. Thus, ECP represents a potential treatment option for this indication, given its good safety profile while maintaining anti-tumor response.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT05700565, https://classic.
CLINICALTRIALS
gov/ct2/show/NCT05700565.
背景
约 11%的免疫相关不良事件 (irAE) 为检查点抑制剂诱导的类固醇难治性 (sr) 和类固醇依赖性 (sd)。由于 irAE 死亡率和/或持续的免疫抑制会损害抗肿瘤反应，这些患者面临更差的结局，尽管这些患者存在 irAE 死亡率和/或持续的免疫抑制，但由于 irAE 死亡率和/或持续的免疫抑制，他们面临着更差的结局，这会损害抗肿瘤反应，但没有基于前瞻性试验数据的既定二线治疗方法。
方法
本前瞻性对照研究调查了体外光化学疗法 (ECP) 作为一种免疫调节疗法在 sr/sd-irAE 中的应用，与二线免疫抑制剂 (SLI) 相比的结果。主要终点是免疫表型的纵向变化；次要终点是 irAE 和肿瘤反应的结果。在基线时、第 1、4、8 和 12 周分析患者的人口统计学数据、生活质量 (EORTC QLQ-C30；全球健康状况 (GHS/QoL)) 和纵向血液样本。
结果
在中期分析时，纳入了 21 名患有 7 种不同 sr/sd-irAE 的患者（11 名接受 ECP，10 名接受 SLI）。与 SLI 组相比，ECP 组的 irAE 临床缓解率更高（93% vs. 80%；95%CI 0.83-1.92；P=0.54），整个随访期间的 GHS/QoL 评分也更好。ECP 患者的总生存率（23 个月 vs. 12 个月；95%CI 0.02-3.02；P=0.27）更高，癌症进展率（33% vs. 67%；95%CI 0.09-1.60；P=0.52）更低。免疫表型分析显示免疫细胞群的变化和免疫检查点的调节。两组均无明显安全性问题。
结论
与 SLI 队列相比，本前瞻性对照研究支持 ECP 在治疗 sr/sd-irAE 方面的临床疗效。因此，鉴于其良好的安全性，同时保持抗肿瘤反应，ECP 为该适应症提供了一种潜在的治疗选择。
试验注册
ClinicalTrials.gov，NCT05700565，https://classic.
临床试验
gov/ct2/show/NCT05700565。
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