Age favoured overall survival in a large population-based Danish patient cohort treated with anti-PD1 immune checkpoint inhibitor for metastatic melanoma
Age favoured overall survival in a large population-based Danish patient cohort treated with anti-PD1 immune checkpoint inhibitor for metastatic melanoma
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DOI：
10.1016/j.ejca.2019.06.022
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发表时间：
2019-09-01
影响因子：
8.4
通讯作者：
Svane, Inge Marie
中科院分区：
文献类型：
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作者：
Bastholt, Lars;Schmidt, Henrik;Svane, Inge Marie
背景和患者：年龄相关免疫功能障碍（ARID）描述了年龄相关的免疫变化，可能影响免疫检查点抑制剂治疗的疗效。我们在丹麦国家转移性黑色素瘤患者队列中评估了ipilimumab（530例患者）或pembrolizumab（562例患者）治疗的疗效。结果：我们确认了已知的与伊匹单抗治疗相关的预后生物标志物，发现年龄对生存或无进展生存没有影响。在接受派姆单抗治疗的患者中，我们也确认了已知的预后生物标志物。与年轻患者相比，70 - 80岁患者的总生存期（OS）和无进展生存期明显更高。在以OS为终点的多变量分析中，年龄被证明是这些患者的独立预后良好的生物标志物。80岁以上患者的生存率并不比年轻患者好，可能是因为显著的合并症增加。结论：我们的分析显示，在70 - 80岁的转移性黑色素瘤患者中，使用靶向PD1的药物生存率更高。在转移性黑色素瘤患者中，ARID似乎不会对检查点抑制剂治疗的疗效产生负面影响。尽管这些数据对老年患者来说令人鼓舞，但临床医生在决定用检查点抑制剂治疗老年患者之前，仍然需要仔细考虑老年患者群体中免疫相关不良事件的更严重后果的更高风险。(C) 2019 Elsevier Ltd.版权所有。
Background and patients: Age-related immune dysfunction (ARID) describes age-associated changes in immunity that may affect the efficacy of immunotherapy with checkpoint inhibitors. We evaluated the efficacy of treatment with ipilimumab (530 patients) or pembrolizumab (562 patients) in a Danish national cohort of metastatic melanoma patients.Results: We confirmed known prognostic biomarkers related to treatment with ipilimumab and found no impact of age on survival or progression-free survival. In patients treated with pembrolizumab, we also confirmed known prognostic biomarkers. Overall survival (OS) and progression-free survival was significantly higher in patients aged between 70 and 80 years compared with younger patients. In multivariate analysis with OS as end-point, age was shown to be an independent good prognostic biomarker in these patients. Survival in patients aged above 80 years was not better than in younger patients, probably because of increase in significant comorbidity.Conclusions: Our analyses have revealed a higher survival rate when using drugs targeting PD1 in metastatic melanoma patients between the age of 70 and 80 years. ARID does not seem to negatively impact the efficacy of treatment with checkpoint inhibitors in metastatic melanoma patients. Despite these encouraging data for elderly patients, clinicians still need to carefully consider the higher risk of more serious outcomes of the immune-related adverse events in the elderly patient population, before deciding to treat old patients with checkpoint inhibitors. (C) 2019 Elsevier Ltd. All rights reserved.