Case Report: Complete Response to Nivolumab in a Patient With Programmed Cell Death 1 Ligand 1-Positive and Multiple Gene-Driven Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitor-Resistant Lung Adenocarcinoma

Front Immunol. 2021 Nov 4:12:686057. doi: 10.3389/fimmu.2021.686057. eCollection 2021.

Abstract

Multiple gene-driven programmed cell death 1 ligand 1 (PD-L1)-expressing non-small-cell lung cancer (NSCLC) is very rare. Previous studies have shown that patients with NSCLC with anaplastic lymphoma kinase (ALK) gene rearrangement rarely benefit from PD-L1 inhibitors. Besides the secondary mutations in ALK gene, other mechanisms might contribute to tumor resistance to ALK tyrosine kinase inhibitors (ALK-TKIs). Herein, we present a case of PD-L1-overexpressing lung adenocarcinoma that harbors both EML4-ALK gene rearrangement and BRAF mutation. In particular, a second molecular analysis after resistance to first- and second-generation ALK-TKIs revealed a high PD-L1 expression and tumor mutation burden. Therefore, treatment with nivolumab monotherapy, an anti-PD-1 inhibitor, was started and the patient achieved complete remission. This case report suggested that PD-1 inhibitors might be an effective treatment option for patients with multiple gene-driven PD-L1-expressing NSCLC harboring ALK gene rearrangement.

Keywords: EML4-ALK; PD-L1; complete remission; lung cancer; nivolumab.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma of Lung / drug therapy*
  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / pathology
  • Adult
  • Anaplastic Lymphoma Kinase / genetics
  • B7-H1 Antigen / genetics
  • Cell Cycle Proteins / genetics
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Microtubule-Associated Proteins / genetics
  • Mutation
  • Nivolumab / pharmacology
  • Nivolumab / therapeutic use*
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins B-raf / genetics
  • Serine Endopeptidases / genetics
  • Treatment Outcome
  • Tumor Microenvironment

Substances

  • B7-H1 Antigen
  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • Protein Kinase Inhibitors
  • Nivolumab
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • EML4 protein, human
  • Serine Endopeptidases