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免疫相关不良事件对接受免疫检查点抑制剂治疗的癌症患者生存的影响:单中心经验及文献综述

Impact of Immune-Related Adverse Events on Immune Checkpoint Inhibitors Treated Cancer Patients' Survival: Single Center Experience and Literature Review.

作者信息

Romão Raquel, Mendes Ana S, Ranchor Ridhi, Ramos Maria João, Coelho João, Pichel Rita Carrilho, Azevedo Sérgio Xavier, Fidalgo Paula, Araújo António

机构信息

Medical Oncology Department, Centro Hospitalar Universitário do Porto, 4099-001 Porto, Portugal.

Oncology Research Unit, UMIB-Unit for Multidisciplinary Research in Biomedicine, ICBAS-School of Medicine and Biomedical Sciences, Universidade do Porto, 4050-346 Porto, Portugal.

出版信息

Cancers (Basel). 2023 Jan 31;15(3):888. doi: 10.3390/cancers15030888.

Abstract

Immune-related adverse events have emerged as a new challenge and its correlation with survival remains unclear. The goal of our study was to investigate the effect of irAE on survival outcomes in solid tumor patients receiving ICI treatment. This was a retrospective, single-center study at a university hospital involving patients with malignancy who received immune checkpoint inhibitors. Chart review was performed on each patient, noting any irAE, including new events or worsening of previous autoimmune condition after starting treatment with ICI. A total of 155 patients were included, 118 (76.1%) were male, with median age of 64 years. Median follow up time was 36 months. Seventy patients (45.2%) had at least one irAE. Of all irAE, nine (8.1%) were classified as grade 3 or higher according to the CTCAE version 5.0. There was one death secondary to pneumonitis. Median ICI cycles until first irAE onset was 4 (range: 2-99). The objective response rate was higher for patients who developed irAE (18.7% vs. 9.0%; = 0.001), as was median overall survival (18 months (95% CI, 8.67-27.32) vs. 10 (95% CI, 3.48-16.52) months; < 0.016) and progression free survival (10 months (95% CI, 5.44-14.56) vs. 3 months (95% CI, 1.94-4.05); = 0.000). The risk of death in patients with irAE was 33% lower when compared to patients without such events (hazard ratio (HR): 0.67; 95% CI, 0.46-0.99; = 0.043). Development of irAE predicted better outcomes, including OS in patients with advanced solid tumors treated with ICI. Further prospective studies are needed to explore and validate this prognostic value.

摘要

免疫相关不良事件已成为一项新挑战,其与生存的相关性仍不明确。我们研究的目的是调查免疫相关不良事件(irAE)对接受免疫检查点抑制剂(ICI)治疗的实体瘤患者生存结局的影响。这是一项在大学医院进行的回顾性单中心研究,纳入接受免疫检查点抑制剂治疗的恶性肿瘤患者。对每位患者进行病历审查,记录任何免疫相关不良事件,包括开始ICI治疗后出现的新事件或既往自身免疫状况的恶化。共纳入155例患者,118例(76.1%)为男性,中位年龄64岁。中位随访时间为36个月。70例患者(45.2%)至少发生过一次免疫相关不良事件。根据CTCAE第5.0版,所有免疫相关不良事件中,9例(8.1%)被分类为3级或更高等级。有1例因肺炎死亡。首次免疫相关不良事件发生前的ICI中位疗程为4个(范围:2 - 99个)。发生免疫相关不良事件的患者客观缓解率更高(18.7%对9.0%;P = 0.001),中位总生存期也更长(18个月(95%CI,8.67 - 27.32)对10个月(95%CI,3.48 - 16.52);P < 0.016),无进展生存期也更长(10个月(95%CI,5.44 - 14.56)对3个月(95%CI,1.94 - 4.05);P = 0.000)。与未发生此类事件的患者相比,发生免疫相关不良事件的患者死亡风险降低33%(风险比(HR):0.67;95%CI,0.46 - 0.99;P = 0.043)。免疫相关不良事件的发生预示着更好的结局,包括接受ICI治疗的晚期实体瘤患者的总生存期。需要进一步的前瞻性研究来探索和验证这种预后价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e8e/9913676/714988b5eb3e/cancers-15-00888-g001a.jpg

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