224P - Germline HLA-I/II is not associated with clinical outcome but the absence of HLA-A01 or the presence of HLA-B27 supertypes were correlated with improved clinical outcome among patients with NSCLC treated with pembrolizumab in combination with chemotherapy

Background

Maximal heterozygosity on the human leukocyte antigen (HLA) loci was found to be associated with improved survival among NSCLC patients treated with immune checkpoint inhibitors (ICI). Here we aimed to investigate the effect of germline HLA-I/-II zygosity on clinical outcomes among NSCLC patients treated with first-line pembrolizumab in combination with chemotherapy. We explored the correlation between different HLA-A/-B supertypes and clinical outcome among the same cohort.

Methods

We prospectively collected pre-treatment blood from patients with NSCLC treated with first-line pembrolizumab in combination with chemotherapy. DNA was extracted from white blood cells and used for high resolution HLA-I/II typing. Genomic HLA-I/II homozygosity was correlated with clinical benefit. We used Sidney et al to classify genomic HLA-A and -B into supertypes.

Results

Of 65 patients recruited, 53 complied with the inclusion criteria. Of those 76%(40/53) have PD-L1 expression of <50% of their cancer cells. Our analysis did not find any association between HLA-I/-II homozygosity and clinical outcome among patients with NSCLC treated with pembrolizumab in combination with chemotherapy. However, the absence of HLA-A01 was associated with favourable PFS (HR=2.09, 95%CI 1.03-4.27, P=0.22) and improved OS (HR=2.58, 95%CI 0.96-6.89, P=0.038). the presence of HLA-B27 was associated with improved PFS (HR=0.24, 95%CI 0.12, P=0.004) but not OS.

Conclusions

The absence of association between genomic HLA-I/-II homozygosity and clinical outcome among patients with advanced NSCLC treated with pembrolizumab in combination with chemotherapy might reflect a diminished role for HLA molecules among patients with low or no PD-L1. HLA-A01 and HLA-B27 might have a role in predicting clinical outcome among this cohort of patients. Further studies are needed to explore biomarkers for this group of patients.

Clinical trial identification

NA

Editorial acknowledgement

Nil

Legal entity responsible for the study

The authors.

Funding

Higher degree by research award scheme provided by Centre for Precision Health at ECU.

Disclosure

M. Millward: Financial Interests, Personal, Advisory Board: BeiGene Australia Pty Ltd, Bristol Myers Squibb Australia Pty Ltd, AstraZeneca Australia Pty Ltd, The Limbic, Eli Lilly Australia Pty Ltd, IQVIA Australia Pty Ltd, Amgen Australia Pty Ltd, Merck Pte Ltd, Pfizer Australia Pty Ltd, Guardant Health, Roche Products Pty Ltd; Financial Interests, Personal, Full or part-time Employment, Employee: University of Western Australia; Financial Interests, Personal, Other, Consultant: Linear Clinical Research; Financial Interests, Institutional, Local PI, Trial payments to Institution: Bristol Myers Squibb, Genentech/Roche, BeiGene, Eli Lilly, Albion Laboratories, Akeso Biopharma, AbbVie, Five Prime Therapeutics, Dizal Pharma, Maxinovel, Amgen, Atridia, INXMED, Alpine Immune Sciences, Turning Point Therapeutics, IMPACT Therapeutics, Kinnate Biopharma, Rely Therapeutics, GenFleet Therapeutics, Vivace Therapeutics, Eucure Biopahrma, InventisBio, Cullinan Oncology, Tyra Biosciences, Axelia Oncology; Non-Financial Interests, Other, Scientific Advisory Committee member: Thoracic Oncology Group Australasia. E.S. Gray: Financial Interests, Personal, Invited Speaker, Invited to present at an MSD event in Melbourne, Australia: MSD Discovery Research Symposium, 28-29th October 2019, Melbourne, Victoria. “Liquid Biopsy for Predicting and Monitoring Response to Immune Checkpoint Blockade in Metastatic Melanoma Patients”: MSD; Financial Interests, Personal, Invited Speaker, Invited to present on a industry sponsored session at ESMO 2022European Society of Medical Oncology, 9-13th September 2022, Paris, France. “Circulating tumour DNA in patients with advanced ovarian cancer receiving neoadjuvant chemo-immunotherapy”: Thermo Fisher Scientific; Financial Interests, Institutional, Research Grant, Grant recipient for the following project:TCR repertoire in combination with HLA and TMB as predictor of response to immune checkpoint blockade in melanoma and lung cancer. Thermo Fisher Scientific Oncomine Clinical Research Grant. 2021. $200,000: Thermo Fisher Scientific. All other authors have declared no conflicts of interest.