Class II Hla-DRB4 Is a Predictive Biomarker for Survival Following Immunotherapy in Metastatic Non-Small Cell Lung Cancer

Authors

Cindy Y Jiang
Lili Zhao
Michael D Green
Shashidhar Ravishankar
Andrea M H Towlerton
Anthony J Scott
Malini Raghavan
Matthew F Cusick
Edus H Warren
Nithya Ramnath

Publication Date

1-3-2024

Journal

Scientific Reports

Abstract

Immune checkpoint inhibitors (ICI) are important treatment options for metastatic non-small cell lung cancer (mNSCLC). However, not all patients benefit from ICIs and can experience immune-related adverse events (irAEs). Limited understanding exists for germline determinants of ICI efficacy and toxicity, but Human Leukocyte Antigen (HLA) genes have emerged as a potential predictive biomarker. We performed HLA typing on 85 patients with mNSCLC, on ICI therapy and analyzed the impact of HLA Class II genotype on progression free survival (PFS), overall survival (OS), and irAEs. Most patients received pembrolizumab (83.5%). HLA-DRB4 genotype was seen in 34/85 (40%) and its presence correlated with improved OS in both univariate (p = 0.022; 26.3 months vs 10.2 months) and multivariate analysis (p = 0.011, HR 0.49, 95% CI [0.29, 0.85]). PFS did not reach significance (univariate, p = 0.12, 8.2 months vs 5.1 months). Eleven patients developed endocrine irAEs. HLA-DRB4 was the predominant genotype among these patients (9/11, 81.8%). Cumulative incidence of endocrine irAEs was higher in patients with HLA-DRB4 (p = 0.0139). Our study is the first to suggest that patients with metastatic NSCLC patients on ICI therapy with HLA-DRB4 genotype experience improved survival outcomes. Patients with HLA-DRB4 had the longest median OS (26.3 months). Additionally, we found a correlation between HLA-DRB4 and the occurrence of endocrine irAEs.

Keywords

Humans, Carcinoma, Non-Small-Cell Lung, HLA-DRB4 Chains, Lung Neoplasms, Nivolumab, Antineoplastic Agents, Immunological, Retrospective Studies, Biomarkers, Immunotherapy, HLA Antigens, Lung cancer, Cancer, Cancer immunotherapy

DOI

10.1038/s41598-023-48546-y

PMID

38172168

PMCID

PMC10764770

PubMedCentral® Posted Date

1-3-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes