Association of HLA class I homozygosity with unfavorable clinical outcomes in patients with non-small cell lung cancer treated with chemo-immunotherapy or immunotherapy as first-line therapy

Dongyup Lee, Jonghanne Park, Horyun Choi, Gahyun Gim, Sukjoo Cho, Leeseul Kim, Youjin Oh, Cyra Y. Kang, Yeseul Kim, Dean Tan, Pedro Antonio Hermida de Viveiros, Young Kwang Chae*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Homozygosity at HLA-I locus has been reported to be an unfavorable predictive biomarker of second-line or beyond immunotherapy in patients with different types of cancer. The linkage between HLA-I zygosity and survival in NSCLC patients treated with first-line immunotherapy with or without chemotherapy has not been reported. Methods: Next generation sequencing with HLA genotyping was performed on patients with advanced NSCLC treated with immune checkpoint inhibitors with or without chemotherapy as first-line (N = 29). Progression free survival was compared between HLA-I homozygous (defined as homozygosity in at least one locus A, B, or C) and heterozygous patients. Kaplan-Meier curves were built, and log-rank test was used. Results: Among 29 enrollees, 25 patients (86.2%) were HLA-I heterozygous and four patients (13.8%) were HLA-I homozygous. Treatment response was not available in five patients with HLA-I heterozygosity. Among 20 patients with HLA-I heterozygosity, five patients (20.0%) had partial response, 10 patients (50.0%) had stable disease, two patients (8.0%) had non-complete response/non-progressive disease, and three patients (12.0%) had progressive disease. Among four patients with HLA-I heterozygosity, one patient (25.0%) had partial response, one patient (25.0%) had stable disease, and two patients (50.0%) had progressive disease. The median progression free survival was not reached in heterozygous group and was 2.97 months in homozygous group (Log-rank p = 0.68). Conclusions: We observed a trend toward an inverse association between HLA-I homozygosity and survival outcomes in patients with NSCLC treated with first-line therapy in conjunction with immunotherapy. Further prospective studies to validate aforementioned relationship are warranted.

Original languageEnglish (US)
Article numbere07916
JournalHeliyon
Volume7
Issue number9
DOIs
StatePublished - Sep 2021

Keywords

  • Heterozygosity
  • Human leukocyte antigen
  • Immunotherapy
  • Non-small cell lung cancer

ASJC Scopus subject areas

  • General

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