Data from HLA-I Evolutionary Divergence Confers Response to PD-1 Blockade plus Chemotherapy in Untreated Advanced Non–Small Cell Lung Cancer

• DOI: 10.1158/1078-0432.c.6762579.v2
• Publication Date: 2024-09-16T12:46:34Z
• Authors: Tao Jiang; Qiqi Jin; Jiahao Wang; Fengying Wu; Jian Chen; Gongyan Chen; Yunchao Huang; Jianhua Chen; Ying Cheng; QiMing Wang; Yueyin Pan; Jianying Zhou; Jianhua Shi; Xingxiang Xu; LiZhu Lin; Wei Zhang; Yiping Zhang; Yunpeng Liu; Yong Fang; Jifeng Feng; Zhehai Wang; Sheng Hu; Jian Fang; Yongqian Shu; Jiuwei Cui; Yi Hu; Wenxiu Yao; Xingya Li; Xiaoyan Lin; Rui Wang; Yongsheng Wang; Wei Shi; Gaohua Feng; Jun Ni; Beibei Mao; Dandan Ren; Huaibo Sun; Henghui Zhang; Luonan Chen; Caicun Zhou; Shengxiang Ren
• Keywords: Divergence (linguistics)

<div>AbstractPurpose:<p>PD-1 blockade plus chemotherapy has become the new standard of care in patients with untreated advanced non–small cell lung cancer (NSCLC), whereas predictive biomarkers remain undetermined.</p>Experimental Design:<p>We integrated clinical, genomic, and survival data 427 NSCLC treated first-line PD-1 or from two phase III trials (CameL CameL-sq) investigated prognostic value HLA class I evolutionary divergence (HED).</p>Results:<p>High HED could predict significantly improved objective response rate (ORR), progression-free (PFS), overall (OS) those who received [in CameL trial, ORR: 81.8% vs. 53.2%; <i>P</i> = 0.032; PFS: hazard ratio (HR), 0.47; 0.012; OS: HR, 0.40; 0.014; CameL-sq 89.2% 62.3%; 0.007; 0.49; 0.005; 0.38; 0.002], but not chemotherapy. In multivariate analysis adjusted for PD-L1 expression tumor mutation burden, high was independently associated markedly better ORR, PFS, OS both trials. Moreover, joint utility showed performance than either alone predicting treatment benefit Single-cell RNA sequencing 58,977 cells collected 11 revealed that tumors had antigen presentation T cell–mediated antitumor immunity, indicating an inflamed microenvironment phenotype.</p>Conclusions:<p>These findings suggest portend chemotherapy.</p><p><i><a href="https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-23-2152" target="_blank">See related commentary by Dimou, p. 4706</a></i></p></div>