Coexistence of a novel NBEA-ALK, EML4-ALK double-fusion in a lung adenocarcinoma patient and response to alectinib: A case report

Lung Cancer. 2021 Dec:162:86-89. doi: 10.1016/j.lungcan.2021.10.015. Epub 2021 Nov 5.

Abstract

Objectives: The echinoderm microtubule-associated protein-like 4 gene (EML4) and anaplastic lymphoma kinase gene (ALK) fusion is the most common ALK rearrangements in non-small cell lung cancer (NSCLC). Herein, we firstly report that coexistence of a novel Neurobeachin (NBEA)-ALK, EML4-ALK double-fusion is sensitive to alectinib.

Materials and methods: Hematoxylin-eosin staining (HE), fluorescent in situ hybridization (FISH), and next-generation sequencing (NGS) was performed on the biopsy sample.

Results: The patient responded to alectinib as a second-line treatment and achieved stable disease for 11 months, without significant symptoms of toxicity. Significantly, the liquid biopsy also validated clinical benefit, with the disappearance of NBEA-ALK and EML4-ALK fusion variants. We also provided a comprehensive review of all 50 ALK fusion genes in NSCLC.

Conclusion: This is the first report on one patient with a novel NBEA-ALK, EML4-ALK double-ALK fusion beneficial from alectinib. Alectinib may be a viable therapeutic option for NSCLC patients with double-ALK fusion, and liquid biopsy could dynamically monitor clinical curative effect.

Keywords: Anaplastic lymphoma kinase (ALK); Case report; Echinoderm microtubule-associated protein-like 4 gene (EML4); Neurobeachin (NBEA); Non-small cell lung cancer (NSCLC).

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenocarcinoma of Lung* / drug therapy
  • Adenocarcinoma of Lung* / genetics
  • Anaplastic Lymphoma Kinase / genetics
  • Carbazoles
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carrier Proteins
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Nerve Tissue Proteins
  • Oncogene Proteins, Fusion / genetics
  • Piperidines
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Carbazoles
  • Carrier Proteins
  • EML4-ALK fusion protein, human
  • NBEA protein, human
  • Nerve Tissue Proteins
  • Oncogene Proteins, Fusion
  • Piperidines
  • Protein Kinase Inhibitors
  • Anaplastic Lymphoma Kinase
  • alectinib