301MO - Genomic HLA as a predictive biomarker for survival among non-small cell lung cancer patient treated with single agent immunotherapy

Background

We aimed to assess the role of genomic HLA-I/II homozygosity in the overall survival benefit in patients with unresectable locally advanced, metastatic non-small lung cancer treated by single agent PD1/PDL1 inhibitors.

Methods

We collected blood from 170 advanced lung cancer patients treated with immunotherapy at two major oncology centres in Western Australia. High quality DNA was extracted from white blood cells and used for HLA-I/II typing. We correlated between genomic HLA-I/II, overall survival (OS) and progression free survival (PFS) in a univariate analysis using a log rank test. Multivariate analysis was performed between HLA-I, OS and PFS including all the variables that influenced the effect of HLA-I homozygosity on OS in the subgroup analysis (age, PD-L1 expression, ECOG and therapy modality) using Cox regression analysis. We then investigated the correlation between indivdual HLA-A and -B supertypes with OS using log rank analysis.

Results

Homozygosity at one or more HLA-I loci and type of checkpoint inhibitor used (anti-PD1 vs anti-PDL1) were the only statistically significant independent predictor of shorter OS (HR=2.17, 95%CI 1.13-4.17, P=0.02 and HR=3.16, 95%CI 1.66-5.99 respectively) in the univariate analysis. This was more significant in patients with tumour expressing PDL1 in more than 50% of cancer cells (HR=3.93, 95%CI 1.30-11.85, P<0.001). In the multivariate analysis, pre-treatment neutrophil to lymphocyte ratio (NLR) also emerged as a prognostic marker of OS (HR=2.17, 95% CI 1.12-4.20, P=0.02) together with HLA-I genotype (HR=2.07, 95% CI 1.07-4.01, P=0.03). The adverse effect of homozygosity at one or more HLA-I loci on PFS was only apparent after controlling for interactions between PD-L1 status and HLA-I genotype (HR= 2.37, 95%CI 1.12 – 5.01, P=0.02). No interactions were found between HLA-I and therapy type, neither its inclusion affected multivariate analysis results. The presence of HLA-A02 supertype was the only type of HLA-I supertypes to be associated with improved OS (HR=0.56 95%CI 0.34-0.93, P=0.023). Table: 301MO

Conclusions

Homozygosity at one or more HLA-I loci was correlated with worse OS and PFS in patients with advanced or metastatic NSCLC treated with single agent immunotherapy. This is mainly in patients with tumours expressing PDL1 in more than 50% of cancer cells. HLA-A02 supertypes is the only positively influencing HLA-I supertype on OS.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.