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高剂量白细胞介素-2 和干扰素作为转移性黑色素瘤的一线免疫治疗:一项大型未选择丹麦患者队列的长期随访。

High-dose interleukin-2 and interferon as first-line immunotherapy for metastatic melanoma: long-term follow-up in a large unselected Danish patient cohort.

机构信息

Department of Clinical Oncology, Odense University Hospital, Odense, Denmark.

Center for Cancer Immune Therapy, Department of Oncology and Haematology, Copenhagen University Hospital, Herlev, Denmark.

出版信息

Eur J Cancer. 2019 Jul;115:61-67. doi: 10.1016/j.ejca.2019.03.023. Epub 2019 May 17.

DOI:10.1016/j.ejca.2019.03.023
PMID:31108244
Abstract

BACKGROUND AND PATIENTS

Between January 2007 and April 2014, 464 Danish patients received high-dose (HD) interleukin-2 (IL-2) and interferon (IFN) as first-line treatment for metastatic melanoma. Our data represent the largest cohort of patients with metastatic melanoma worldwide, with relevant data on all patients and no patients lost to follow-up. Data have been gathered in a national database on the treatment of metastatic melanoma established since 2011.

RESULTS

One hundred eighteen patients (25%) obtained an objective response rate (ORR) to treatment with a median progression-free survival (PFS) of 3.4 months and a median overall survival (OS) of 14.2 months. Furthermore, 2-, 3- and 5-year survival was 32.0%, 23.2% and 16.6%, respectively. Ipilimumab as second-line therapy has been used since July 2010. We divided patients in two subgroups before and after this date to evaluate the effects of new treatment strategies. Patient characteristics, ORR and PFS were comparable in the two subgroups. Survival was significantly improved after 2010, with an increase in median OS from 12.2 to 16.0 months and in 5-year OS from 12.5% to 20.7%.

CONCLUSIONS

Our data confirm that HD IL-2/IFN as first-line therapy in metastatic melanoma leads to long-term survival in a subset of treated patients. Potentially, IL-2/IFN might represent a treatment option in patients with active melanoma after established initial treatment with checkpoint inhibitors and BRAF/MEK-targeted therapies.

摘要

背景与患者

2007 年 1 月至 2014 年 4 月,464 名丹麦患者接受了高剂量(HD)白细胞介素-2(IL-2)和干扰素(IFN)作为转移性黑色素瘤的一线治疗。我们的数据代表了全球转移性黑色素瘤患者中最大的队列,所有患者都有相关数据,且无患者失访。这些数据是从 2011 年建立的转移性黑色素瘤治疗国家数据库中收集的。

结果

118 名患者(25%)对治疗有客观反应率(ORR),无进展生存期(PFS)的中位数为 3.4 个月,总生存期(OS)的中位数为 14.2 个月。此外,2、3 和 5 年生存率分别为 32.0%、23.2%和 16.6%。自 2010 年 7 月以来,已将依匹单抗作为二线治疗药物。我们将患者分为两个亚组,以评估新治疗策略的效果。两个亚组患者的特征、ORR 和 PFS 相似。2010 年后生存情况显著改善,中位 OS 从 12.2 个月增加到 16.0 个月,5 年 OS 从 12.5%增加到 20.7%。

结论

我们的数据证实,转移性黑色素瘤的 HD IL-2/IFN 作为一线治疗可使一部分治疗患者获得长期生存。潜在地,IL-2/IFN 可能代表了在已接受检查点抑制剂和 BRAF/MEK 靶向治疗的患者中治疗活跃型黑色素瘤的一种治疗选择。

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