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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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Hyperprogressive disease during PD-1/PD-L1 blockade in patients with non-small-cell lung cancer

C G Kim1, K H Kim2, K-H Pyo3

  • 1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon; Division of Medical Oncology, Department of Internal Medicine.

Annals of Oncology : Official Journal of the European Society for Medical Oncology
|April 13, 2019
PubMed
Abstract

Insights

Hyperprogressive disease (HPD) affects nearly 21% of non-small-cell lung cancer (NSCLC) patients treated with Programmed cell death 1 (PD-1)/PD-L1 inhibitors. Lower effector/memory CD8+ T cells and higher exhausted TIGIT+ T cells predict HPD and poorer survival.

Area of Science:

  • Oncology
  • Immunotherapy
  • Cancer Research

Background:

  • Programmed cell death 1 (PD-1)/PD-L1 inhibitors are standard for non-small-cell lung cancer (NSCLC).
  • Hyperprogressive disease (HPD), an accelerated tumor growth, is an emerging adverse effect of PD-1/PD-L1 blockade.
  • HPD is associated with poor prognosis in NSCLC patients.

Purpose of the Study:

  • To determine the incidence of HPD in NSCLC patients receiving PD-1/PD-L1 inhibitors.
  • To identify clinical or immunologic factors associated with HPD.
  • To explore the prognostic significance of HPD.

Main Methods:

  • Retrospective analysis of 263 NSCLC patients treated with PD-1/PD-L1 inhibitors.
  • HPD definition based on tumor growth kinetics (TGK), tumor growth rate (TGR), and time to treatment failure (TTF).
  • Immunophenotyping of peripheral blood CD8+ T lymphocytes for potential biomarkers.

Main Results:

  • HPD incidence ranged from 20.5% to 37.3% based on different criteria.
  • HPD was significantly associated with worse progression-free survival and overall survival.
  • No specific clinicopathologic variables predicted HPD; however, immune biomarkers (CD8+ T cell subsets) showed association.

Conclusions:

  • HPD is a frequent complication of PD-1/PD-L1 blockade in NSCLC.
  • Immune cell profiling may help predict HPD and patient outcomes.
  • Further research into HPD mechanisms and predictive biomarkers is warranted.
Keywords:
NSCLCPD-1/PD-L1 blockadebiomarkershyperprogressive diseasetumor growth dynamics

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