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迟发性中度毒性是个好兆头:检查点抑制剂免疫治疗中毒性与生存的关联——单中心经验

Moderate toxicity with late onset as a good omen: association between toxicity and survival in the checkpoint inhibitor immunotherapy-a single center experience.

作者信息

Rudzińska Anna, Juchaniuk Pola, Oberda Jakub, Krukowska Kamila, Krzyśkowska Sylwia, Kuchta Eliza, Rodzajewska Anna, Janiszewska Mariola, Machulska-Ciuraj Katarzyna, Szklener Katarzyna

机构信息

Department of Clinical Oncology and Chemotherapy, Medical University of Lublin, Lublin, Poland.

Department of Medical Informatics and Statistics with e-Health Lab, Medical University of Lublin, Lublin, Poland.

出版信息

Front Immunol. 2025 Apr 28;16:1527103. doi: 10.3389/fimmu.2025.1527103. eCollection 2025.

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by enhancing T-cell-mediated immune responses against tumors. However, their use can lead to immune-related adverse events (irAEs) impacting patient outcomes. This single-center, observational study investigates the relationship between immune-related adverse events (irAEs) and survival outcomes and, to our knowledge, is the first of this kind in Polish population. Data of the 151 patients treated with ICIs, with or without chemotherapy, at the Department of Clinical Oncology and Chemotherapy in the Independent Public Hospital No. 4 in Lublin were collected from electronic medical records. Statistical analyses were performed using the Kaplan-Meier estimator, log-rank test, and multivariable Cox proportional hazard model (p < 0.05). IrAEs were observed in 38% of the patients, with the most common being thyroid dysfunction (11.9%) and dermal toxicity (6.6%). The median OS for patients with irAEs was 18.7 months, compared to 13.6 months for those without irAEs, though the difference was not statistically significant (p = 0.284). Patients with moderate toxicity had the highest median OS (26 months), while those with severe toxicity had a median OS of 6.41 months. Late-onset irAEs were associated with improved OS and PFS. Pack-years of smoking significantly impacted both OS ( = 1.01, p = 0.014) and PFS ( = 1.01, p = 0.011). Despite results not reaching statistical significance, the findings emphasize the clinical relevance of irAEs in treatment optimization and warrant further research to better understand their role in patient outcomes.

摘要

免疫检查点抑制剂(ICIs)通过增强T细胞介导的抗肿瘤免疫反应,彻底改变了癌症治疗方法。然而,使用这些药物可能会导致免疫相关不良事件(irAEs),影响患者的治疗结果。本单中心观察性研究调查了免疫相关不良事件(irAEs)与生存结果之间的关系,据我们所知,这是波兰人群中的首例此类研究。从卢布林市第4独立公立医院临床肿瘤学和化疗科的电子病历中收集了151例接受ICIs治疗(无论是否联合化疗)患者的数据。使用Kaplan-Meier估计器、对数秩检验和多变量Cox比例风险模型进行统计分析(p<0.05)。38%的患者观察到irAEs,最常见的是甲状腺功能障碍(11.9%)和皮肤毒性(6.6%)。发生irAEs的患者的中位总生存期(OS)为18.7个月,未发生irAEs 的患者为13.个月,尽管差异无统计学意义(p=0.284)。中度毒性患者的中位OS最高(26个月),而重度毒性患者的中位OS为6.41个月。迟发性irAEs与OS和无进展生存期(PFS)的改善相关。吸烟包年数对OS(=1.01,p=0.014)和PFS(=1.01,p=0.011)均有显著影响。尽管结果未达到统计学意义,但研究结果强调了irAEs在优化治疗中的临床相关性,值得进一步研究以更好地了解它们在患者治疗结果中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/073c/12066656/76fbddf87570/fimmu-16-1527103-g001.jpg

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