辅助免疫疗法在 III 期和可切除 IV 期黑色素瘤老年患者中的应用：来自荷兰黑色素瘤治疗登记处的毒性和无复发生存结局。

Adjuvant immunotherapy in older patients with stage III and resected stage IV melanoma: Toxicity and recurrence-free survival outcomes from the Dutch melanoma treatment registry.

机构信息

Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, Leiden 2333ZA, the Netherlands.

Department of Gerontology and Geriatrics, Leiden University Medical Center, Albinusdreef 2, Leiden 2333ZA, the Netherlands.

出版信息

Eur J Cancer. 2024 Nov;212:115056. doi: 10.1016/j.ejca.2024.115056. Epub 2024 Sep 30.

DOI:10.1016/j.ejca.2024.115056

PMID:39368226

Abstract

BACKGROUND

Adjuvant anti-PD-1 therapy improves relapse free survival in stage III melanoma, but also leads to immune-related adverse events (irAEs). Older patients are of particular interest due to comorbidities and frailty, which may impact their ability to tolerate irAEs and benefit from anti-PD-1 therapy. This study aimed to explore associations between clinical parameters and the occurrence of grade ≥ 3 irAEs and recurrence-free survival (RFS) in older patients with radically resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy.

METHODS

Patients aged ≥ 65 with resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy between 2018 and 2022 were selected using real-world data from the nationwide Dutch Melanoma Treatment Registry (DMTR). A univariate and multivariable logistic regression was used to compare determinants of grade ≥ 3 irAEs, and univariate and multivariable Cox-proportional hazard models were fitted to identify factors influencing RFS.

RESULTS

The study included 885 patients, with 280 aged 75 and older. The incidence of grade ≥ 3 irAEs was 15.5 % in the 65-74 age group and 13.9 % in the ≥ 75 age group. No significant correlation was found between age and grade ≥ 3 irAEs. However, an increasing number of comorbidities was associated with a higher risk of grade ≥ 3 irAEs (multivariable analyses: OR 1.83, 95 % C.I. 0.99-3.40). The 1-year RFS rate of 80.0 % of this study was comparable to those reported in previous registration trials and real-world data. Having ≥ 3 comorbidities was significantly associated with a decrease in RFS (HR: 1.68, 95 % C.I. 1.15-2.44).

CONCLUSION

Older patients had similar benefit of adjuvant immunotherapy compared to older subgroups in previous trials. However, patients with multiple comorbidities were at increased risk of grade ≥ 3 irAEs and had a lower RFS. This should be considered when deciding upon adjuvant treatment.

摘要

背景

辅助抗 PD-1 治疗可改善 III 期黑色素瘤的无复发生存期，但也会导致免疫相关不良事件（irAEs）。由于合并症和虚弱，老年患者尤其受到关注，这可能会影响他们对 irAEs 的耐受能力和从抗 PD-1 治疗中获益的能力。本研究旨在探讨临床参数与接受辅助抗 PD-1 治疗的根治性切除 III 期/IV 期皮肤黑色素瘤老年患者发生≥3 级 irAEs 和无复发生存期（RFS）之间的关系。

方法

本研究使用全国性荷兰黑色素瘤治疗登记处（DMTR）的真实世界数据，选择了 2018 年至 2022 年期间接受辅助抗 PD-1 治疗的年龄≥65 岁、接受根治性切除 III 期/IV 期皮肤黑色素瘤治疗的患者。使用单变量和多变量逻辑回归比较了发生≥3 级 irAEs 的决定因素，并拟合单变量和多变量 Cox 比例风险模型以确定影响 RFS 的因素。

结果

本研究共纳入 885 例患者，其中 280 例年龄≥75 岁。65-74 岁年龄组和≥75 岁年龄组≥3 级 irAEs 的发生率分别为 15.5%和 13.9%。年龄与≥3 级 irAEs 之间无显著相关性。然而，合并症数量的增加与发生≥3 级 irAEs 的风险增加相关（多变量分析：OR 1.83，95%CI 0.99-3.40）。本研究的 1 年 RFS 率为 80.0%，与之前的登记试验和真实世界数据报告的结果相当。存在≥3 种合并症与 RFS 下降显著相关（HR：1.68，95%CI 1.15-2.44）。