Prognostic value of HLA-I homozygosity in patients with non-small cell lung cancer treated with single agent immunotherapy

Afaf Abed; Leslie Calapre; Johnny Lo; Suzana Correia; Samantha Bowyer; Abha Chopra; Mark Watson; Muhammad Adnan Khattak; Michael Millward; Elin Solomonovna Gray

doi:10.1136/jitc-2020-001620

Prognostic value of HLA-I homozygosity in patients with non-small cell lung cancer treated with single agent immunotherapy

J Immunother Cancer. 2020 Nov;8(2):e001620. doi: 10.1136/jitc-2020-001620.

Authors

Afaf Abed^{1

2

3}, Leslie Calapre⁴, Johnny Lo⁴, Suzana Correia³, Samantha Bowyer^{2

5}, Abha Chopra⁶, Mark Watson⁶, Muhammad Adnan Khattak^{4

3}, Michael Millward^{2

5

7}, Elin Solomonovna Gray⁴

Affiliations

¹ School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia afaf.abed@health.wa.gov.au.
² Linear Clinical Research, Nedlands, Western Australia, Australia.
³ Department of Medical Oncology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia.
⁴ School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
⁵ Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
⁶ Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
⁷ School of Medicine, The University of Western Australia, Perth, Western Australia, Australia.

Abstract

Background: We aimed to assess the impact of genomic human leukocyte antigen (HLA)-I/II homozygosity on the survival benefit of patients with unresectable locally advanced, metastatic non-small lung cancer treated by single-agent programmed cell death protein-1/programmed death ligand 1 (PD1/PDL1) inhibitors.

Methods: We collected blood from 170 patients with advanced lung cancer treated with immunotherapy at two major oncology centers in Western Australia. Genomic DNA was extracted from white blood cells and used for HLA-I/II high-resolution typing. HLA-I/II homozygosity was tested for association with survival outcomes. Univariable and multivariable Cox regression models were constructed to determine whether HLA homozygosity was an independent prognostic factor affecting Overall Survival (OS) and Progression Free Survival (PFS). We also investigated the association between individual HLA-A and -B supertypes with OS.

Results: Homozygosity at HLA-I loci, but not HLA-II, was significantly associated with shorter OS (HR=2.17, 95% CI 1.13 to 4.17, p=0.02) in both univariable and multivariable analysis. The effect of HLA-I homozygosity in OS was particularly relevant for patients with tumors expressing PDL1 ≥50% (HR=3.93, 95% CI 1.30 to 11.85, p<0.001). The adverse effect of HLA-I homozygosity on PFS was only apparent after controlling for interactions between PDL1 status and HLA-I genotype (HR=2.21, 95% CI 1.04 to 4.70, p=0.038). The presence of HLA-A02 supertype was the only HLA-I supertype to be associated with improved OS (HR=0.56, 95% CI 0.34 to 0.93, p=0.023).

Conclusion: Our results suggest that homozygosity at ≥1 HLA-I loci is associated with short OS and PFS in patients with advanced non-small cell lung cancer with PDL1 ≥50% treated with single-agent immunotherapy. Carriers of HLA-A02 supertype reported better survival outcomes in this cohort of patients.

Keywords: biomarkers; immunotherapy; lung neoplasms; tumor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Carcinoma, Non-Small-Cell Lung / genetics*
Carcinoma, Non-Small-Cell Lung / mortality
Carcinoma, Non-Small-Cell Lung / pathology
Female
HLA Antigens / genetics*
Humans
Immunotherapy / methods*
Lung Neoplasms / genetics*
Lung Neoplasms / mortality
Lung Neoplasms / pathology
Male
Prognosis
Progression-Free Survival

Substances

HLA Antigens