Primary Resistance to PD-1-Based Immunotherapy-A Study in 319 Patients with Stage IV Melanoma
Primary Resistance to PD-1-Based Immunotherapy-A Study in 319 Patients with Stage IV Melanoma
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DOI：
10.3390/cancers12041027
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发表时间：
2020-04-01
期刊：
影响因子：
5.2
通讯作者：
Garbe, Claus
中科院分区：
文献类型：
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作者：
Amaral, Teresa;Seeber, Olivia;Garbe, Claus
背景：在接受免疫检查点抑制剂治疗的IV期黑色素瘤患者中，约有40%-65%的患者对免疫治疗存在原发耐药性。少数患者接受二线治疗，临床益处很小。患者和方法：对2015年1月至2018年12月期间接受一线PD-1免疫治疗的IV期黑色素瘤患者进行调查。在开始免疫治疗后的第一次肿瘤评估时，主要抵抗被定义为进展性疾病(PD)。完全缓解、部分缓解和病情稳定的患者被归类为疾病控制(DC)。总生存期(OS)和无进展生存期(PFS)采用Kaplan-Meier估计法。采用单因素和多因素Logistic回归分析确定与OS相关的预后因素。结果：共纳入319例患者，其中40%的患者对免疫治疗有原发抵抗。中位随访时间为22个月。原发耐药患者的1年、2年和3年OS率分别为41%、15%和10%，而获得DC的患者分别为91%、81%和65%。下列独立的有意义的OS预后因素被确定：蛋白S100B水平和原发肿瘤的位置。当分析由这两个变量组成的风险组(低、中、高风险亚组)时，OS(p<；0.0001)有统计学上的显著差异，而PFS(p=0.230)无统计学差异。结论：对免疫治疗有原发抵抗的黑色素瘤患者预后很差。与治疗前的危险因素相比，在开始免疫治疗后的第一次肿瘤评估时的反应是对疾病进一步发展的更强的预后因素。
Background: Primary resistance to immunotherapy can be observed in approximately 40-65% of the stage IV melanoma patients treated with immune checkpoint inhibitors. A minority of the patients receive a second-line therapy, and the clinical benefit is small. Patients and methods: Stage IV melanoma patients treated with first-line PD-1-based immunotherapy between January 2015 and December 2018 were investigated. Primary resistance was defined as progressive disease (PD) at the time of the first tumor assessment after starting immunotherapy. Patients with complete response, partial response, and stable disease were classified as having disease control (DC). Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier estimator. Univariate and multivariate logistic regression analyses were performed to determine prognostic factors associated with OS. Results: Three hundred and nineteen patients were included, and 40% had primary resistance to immunotherapy. The median follow-up time was 22 months. Patients with primary resistance had 1-, 2-, and 3-year OS rates of 41%, 15%, and 10%, respectively, compared to 91%, 81%, and 65% for the patients who achieved DC. The following independently significant prognostic factors for OS were identified: protein S100B level and primary tumor localization. There was a statistically significant difference for OS (p < 0.0001) but not for PFS (p = 0.230) when analyzing risk groups formed with a combination of these two variables (low-, intermediate-, and high-risk subgroups). Conclusions: Melanoma patients with primary resistance to immunotherapy have a dismal prognosis. Response at the first tumor assessment after starting immunotherapy is a stronger prognostic factor for the further course of the disease than pretreatment risk factors.