University Côte d'Azur, Centre Antoine Lacassagne, Oncopharmacology Unit, Nice, France.
University Côte d'Azur, Centre Antoine Lacassagne, Epidemiology and Biostatistics Department, Nice, France.
Sci Rep. 2020 Feb 27;10(1):3565. doi: 10.1038/s41598-020-60437-0.
Hyperprogressive disease (HPD), an unexpected acceleration of tumor growth kinetics, is described in cancer patients treated with anti-PD-1/anti-PD-L1 agents. Here, our aim was to take into consideration the host and explore whether single nucleotide polymorphisms (SNPs) in key genes involved in immune response might predispose to HPD. DNA was extracted from blood-samples from 98 patients treated under CPI monotherapy. Four candidate genes (PD-1, PD-L1, IDO1 and VEGFR2) and 15 potential SNPs were selected. The TGK (ratio of the slope of tumor growth before treatment and the slope of tumor growth on treatment) was calculated. Hyperprogression was defined as a TGK≥2. TGK calculation was feasible for 80 patients (82%). HPD was observed for 11 patients (14%) and was associated with shorter overall survival (P = 0.003). In univariate analysis, HPD was significantly associated with age ≥70 y (P = 0.025), immune-related toxicity (P = 0.016), VEGFR2 rs1870377 A/T or A/A (P = 0.005), PD-L1 rs2282055 G/T or G/G (P = 0.024) and PD-L1 rs2227981 G/A or A/A (P = 0.024). Multivariate analysis confirmed the correlation between HPD and age ≥70 y (P = 0.006), VEGFR2 rs1870377 A/T or A/A (P = 0.007) and PD-L1 rs2282055 G/T or G/G (P = 0.018). Immunogenetics could become integral predictive factors for CPI-based immunotherapy.
超进展性疾病（HPD）是指癌症患者在接受抗 PD-1/抗 PD-L1 治疗后肿瘤生长动力学的意外加速。在这里，我们的目的是考虑宿主，并探讨参与免疫反应的关键基因中的单核苷酸多态性（SNP）是否可能导致 HPD。从 98 名接受 CPI 单药治疗的患者的血液样本中提取 DNA。选择了 4 个候选基因（PD-1、PD-L1、IDO1 和 VEGFR2）和 15 个潜在的 SNP。计算了 TGK（治疗前肿瘤生长斜率与治疗期间肿瘤生长斜率的比值）。将 TGK≥2 定义为超进展。80 名患者（82%）的 TGK 计算是可行的。观察到 11 名患者（14%）出现 HPD，且与总生存期较短相关（P=0.003）。在单变量分析中，HPD 与年龄≥70 岁（P=0.025）、免疫相关毒性（P=0.016）、VEGFR2 rs1870377 A/T 或 A/A（P=0.005）、PD-L1 rs2282055 G/T 或 G/G（P=0.024）和 PD-L1 rs2227981 G/A 或 A/A（P=0.024）显著相关。多变量分析证实了 HPD 与年龄≥70 岁（P=0.006）、VEGFR2 rs1870377 A/T 或 A/A（P=0.007）和 PD-L1 rs2282055 G/T 或 G/G（P=0.018）之间的相关性。免疫遗传学可能成为基于 CPI 的免疫治疗的重要预测因素。
