Department of Biomarker and Genome Sciences, Merck & Co., Kenilworth, NJ 07033, USA.
Department of Biostatistics and Research Decision Sciences, Merck & Co., Kenilworth, NJ 07033, USA.
Immunity. 2022 Jan 11;55(1):56-64.e4. doi: 10.1016/j.immuni.2021.12.006. Epub 2022 Jan 5.
We evaluated the impact of class I and class II human leukocyte antigen (HLA) genotypes, heterozygosity, and diversity on the efficacy of pembrolizumab. Seventeen pembrolizumab clinical trials across eight tumor types and one basket trial in patients with advanced solid tumors were included (n > 3,500 analyzed). Germline DNA was genotyped using a custom genotyping array. HLA diversity (measured by heterozygosity and evolutionary divergence) across class I loci was not associated with improved response to pembrolizumab, either within each tumor type evaluated or across all patients. Similarly, HLA heterozygosity at each class I and class II gene was not associated with response to pembrolizumab after accounting for the number of tests conducted. No conclusive association between HLA genotype and response to pembrolizumab was identified in this dataset. Germline HLA genotype or diversity alone is not an important independent determinant of response to pembrolizumab and should not be used for clinical decision-making in patients treated with pembrolizumab.
我们评估了 I 类和 II 类人类白细胞抗原（HLA）基因型、杂合性和多样性对 pembrolizumab 疗效的影响。纳入了 17 项针对晚期实体瘤患者的 pembrolizumab 临床试验（分析了超过 3500 例患者），这些试验涵盖了 8 种肿瘤类型和 1 项篮子试验。使用定制的基因分型阵列对种系 DNA 进行了基因分型。HLA 多样性（通过杂合性和进化分歧来衡量）在 I 类基因座上与 pembrolizumab 的疗效改善无关，无论是在评估的每种肿瘤类型内还是在所有患者中。同样，在考虑到进行的测试数量后，每个 I 类和 II 类基因的 HLA 杂合性与 pembrolizumab 的反应也没有相关性。在该数据集内未确定 HLA 基因型与 pembrolizumab 反应之间的明确关联。在接受 pembrolizumab 治疗的患者中，种系 HLA 基因型或多样性本身并不是反应的重要独立决定因素，不应用于临床决策。
