e-Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2021

HLA-I heterozygosity and increased incidence of immune related toxicity among non-small cell lung cancer (NSCLC) patients treated with single agent immunotherapy (#318)

Ngie Chang Law 1 , Afaf Abed 2
  1. Sir Charles Gairdner Hospital, Nedlands, WA, Australia
  2. Edith Cowan University, Joondalup, WA, Australia

Background

Immune-mediated adverse events (IRAE) result in treatment cessation and negatively impact on immunotherapy efficacy among NSCLC patients treated with immunotherapy. Predicting those who are more likely to experience IRAE may help to reduce morbidity and mortality associated with IRAE. While strong associations between human leucocyte antigen (HLA) and autoimmune disease is well documented, the association between HLA and IRAE among NSCLC is unclear.

Methods

We collected blood from 179 NSCLC patients treated with anti-PD1/PDL1 in the first- or second-line setting. DNA was extracted from peripheral blood samples collected and high quality HLA typing performed. Toxicity data was collected via electronic medical records and graded as per common terminology criteria for adverse event (CTCAE) v5.0. Univariate analysis using GraphPad Prism was used to correlate between HLA-I/II heterozygosity with toxicity using Fisher’s exact test. We investigated the relationship between toxicity, overall response rate (ORR), progression free survival (PFS) and overall survival (OS). In addition, we investigated the relationship between different HLA-I supertypes and toxicity as well as correlated heterozygosity at all HLA-I loci with different types of IRAE.

Results

Heterozygosity at all HLA-I, but not HLA-II loci was associated with increased risk of IRAE with relative risk RR= 2.19 (95%CI 1.12-4.42, P=0.016). All patients with any grade pneumonitis (15/179, 8.4%) and those with G3 toxicity (17/179, 9.5%) were heterozygous at all HLA-I loci (P=0.037, 0.023). The occurrence of IRAE in an individual was associated with improved PFS (HR= 1.36, 95%CI 0.93-2.05, P= 0.031) but not ORR or OS. None of HLA-I supertypes seems to influence the occurrence of toxicity in an individual.

Conclusions

Heterozygosity at all HLA-I loci can be a useful biomarker to predict IRAE among NSCLC patients treated with anti-PD1/PD-L1 in the first- or second-line setting. This is more important among patients who developed pneumonitis or Grade 3 toxicities.