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

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. 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. 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. 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.