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Mark Watson



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    FP12 - Tumor Biology and Systems Biology - Basic and Translational Science (ID 188)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Tumor Biology and Systems Biology - Basic and Translational Science
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP12.07 - Prognostic Value of HLA-I Homozygosity in Non-Small Cell Lung Cancer Patients Treated with Single Agent Immunotherapy (ID 1069)

      00:00 - 00:00  |  Author(s): Mark Watson

      • Abstract
      • Slides

      Introduction

      HLA plays a key role on the orchestration of the immune response. In particular, HLA downregulation is a well-established mechanism in cancer immune evasion. On the other hand, the role of HLA homozygosity in cancer control and response to immunotherapy is less well understood. We aimed to assess the impact of genomic HLA-I/II homozygosity in the survival benefit of 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. 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. Univariate and multivariate Cox regression models were constructed to determine where 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 a statistically significant associated with shorter OS (HR=2.17, 95%CI 1.13-4.17, P=0.02) in both univariate and multivariate analysis. The effect HLA-I homozygosity in OS was particularly relevant for patients with tumours expressing PDL1 ≥50% (HR=3.93, 95%CI 1.30-11.85, P<0.001). The adverse effect of HLA-I hhomozygosity on PFS was only apparent after controlling for interactions between PD-L1 status and HLA-I genotype (HR= 2.21, 95%CI 1.04 – 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 0.34-0.93, P=0.023)

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      Conclusion

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

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