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Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients
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PD-L1 Expression, Tumor Mutational Burden, and Cancer Gene Mutations Are Stronger Predictors of Benefit from Immune

Marcelo V Negrao1, Vincent K Lam1, Alexandre Reuben1

  • 1Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
|February 20, 2019
PubMed
Abstract

Insights

Human leukocyte antigen (HLA) class I genotype did not impact survival in non-small cell lung cancer (NSCLC) patients receiving immune checkpoint blockade (ICB). Other tumor markers are more predictive of ICB treatment outcomes in NSCLC.

Area of Science:

  • Immunogenomics
  • Oncology
  • Translational Research

Background:

  • Immune checkpoint blockade (ICB) has transformed non-small cell lung cancer (NSCLC) treatment, yet durable responses are limited to a subset of patients.
  • Understanding resistance mechanisms is crucial for improving ICB efficacy.
  • Human leukocyte antigen (HLA) class I heterozygosity has been proposed as a potential factor influencing ICB response.

Purpose of the Study:

  • To investigate the association between HLA class I genotype and treatment outcomes in NSCLC patients receiving ICB.
  • To determine if HLA class I heterozygosity or specific HLA alleles/supertypes predict response to ICB in NSCLC.

Main Methods:

  • Collected HLA typing, genomic, and clinical data from advanced NSCLC patients treated with ICB.
  • Compared progression-free survival (PFS) and overall survival (OS) between HLA class I-heterozygous and -homozygous patients.
  • Validated findings in two independent NSCLC cohorts (CheckMate-012 and Chowell).

Main Results:

  • No significant correlation was found between HLA class I zygosity and PFS or OS across all three cohorts (M. D. Anderson, CheckMate-012, Chowell).
  • No specific HLA class I supertype or allele consistently predicted survival outcomes.
  • Predictors of worse outcomes included targetable driver mutations, STK11 mutations, PD-L1 negativity, and low tumor mutational burden.

Conclusions:

  • HLA class I genotype does not appear to be a reliable predictor of survival in advanced NSCLC patients treated with ICB.
  • The influence of HLA class I diversity on ICB response may be cancer-type specific.
  • Tumor genomic and immune markers are more significant predictors of ICB efficacy in NSCLC.
Keywords:
HLA class IImmunotherapyLung cancerPD-L1Tumor mutational burden

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