A novel HLA-DQB2::MET gene fusion variant in lung adenocarcinoma with prolonged response to tepotinib: a case report

Douglas Dias E Silva; Isa Mambetsariev; Jeremy Fricke; Razmig Babikian; Shaira Therese Dingal; Farhad Mazdisnian; Behnam Badie; Leonidas Arvanitis; Michelle Afkhami; Miguel Villalona-Calero; Ravi Salgia

doi:10.21037/tlcr-24-34

A novel HLA-DQB2::MET gene fusion variant in lung adenocarcinoma with prolonged response to tepotinib: a case report

Transl Lung Cancer Res. 2024 May 31;13(5):1163-1168. doi: 10.21037/tlcr-24-34. Epub 2024 May 29.

Affiliations

¹ Department of Medical Oncology and Therapeutic Research, City of Hope National Medical Center, Duarte, CA, USA.
² Department of Medical Oncology, Hospital Israelita Albert Einstein, Sao Paulo, Brazil.
³ Department of Medicine, City of Hope, Duarte, CA, USA.
⁴ Department of Surgery, City of Hope, Duarte, CA, USA.
⁵ Department of Pathology, City of Hope, Duarte, CA, USA.

Abstract

Background: MET rearrangements are infrequently observed in non-small cell lung cancer (NSCLC). Advanced genomic detection techniques have unveiled such infrequent genomic variations, particularly MET fusions in approximately 0.5% of NSCLC patients. Tyrosine kinase inhibitors (TKIs) have revolutionized the standard of care in lung cancer and more recently a second generation MET TKI tepotinib received Food and Drug Administration (FDA) approval for MET exon 14 alterations in metastatic NSCLC. Despite this, the therapeutic landscape for MET-rearranged NSCLC patients remains significantly unexplored. The aim of our report is to detail a unique case of a patient with metastatic lung adenocarcinoma with a novel HLA-DQB2::MET fusion detected by next-generation sequencing (NGS) following previous treatment resistance.

Case description: A 73-year-old female was initially started on carboplatin, pemetrexed and pembrolizumab with maintenance, but eventually had progression in the left upper lobe (LUL). Upon progression she was enrolled in a clinical trial of a monoclonal antibody with or without a PD-1 inhibitor, but brain metastasis progression was eventually detected by magnetic resonance imaging (MRI) requiring stereotactic radiosurgery (SRS) and a craniotomy. The trial drug was eventually discontinued due to progression and toxicity and NGS on bronchoscopy tissue revealed HLA-DQB2::MET fusion. The patient was initiated on tepotinib and continues with clinical and radiological stable disease for over 12 months. The patient's response to a MET inhibitor, tepotinib, underscores the potential efficacy of selective MET inhibitors for individuals with previously unexplored MET fusions.

Conclusions: The positive response to tepotinib of a patient with NSCLC harboring a novel MET-Fusion underscores the importance of the use of comprehensive next-generational sequencing-based panels and highlights the necessity for additional research and clinical exploration of selective MET inhibitors for managing NSCLC with MET rearrangements.

Keywords: HLA-DQB2::MET fusion; Non-small cell lung cancer (NSCLC); case report; targeted therapy; tepotinib.

Publication types

Case Reports