Joint DNA-RNA-based NGS for diagnosis and treatment of a rare CD47-MET fusion lung adenocarcinoma which was immunoresistant and savoltinib-sensitive: a case report

• Published in: Frontiers in immunology 2024-06, Vol.15, p.1386561
• Main Authors: Wang, Rulan, Liu, Yanyang, Yu, Xuejiao, Wang, Weiya, Liu, Jiewei
• Format: Article
• Language: English
• Subjects: Adenocarcinoma of Lung - diagnosis; Adenocarcinoma of Lung - drug therapy; Adenocarcinoma of Lung - genetics; Adenocarcinoma of Lung - immunology; Adenocarcinoma of Lung - therapy; Adult; case report; CD47-MET fusion; Drug Resistance, Neoplasm - genetics; Female; High-Throughput Nucleotide Sequencing; Humans; Immune Checkpoint Inhibitors - therapeutic use; immune microenvironment; Immunology; Lung Neoplasms - diagnosis; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - therapy; MET p D1228H; non-small cell lung cancer; Oncogene Proteins, Fusion - genetics; Proto-Oncogene Proteins c-met - genetics; savolitinib
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1386561

Targeted therapy and immunotherapy are both important in the treatment of non-small-cell lung cancer (NSCLC). Accurate diagnose and precise treatment are key in achieving long survival of patients. fusion is a rare oncogenic factor, whose optimal detection and treatment are not well established. Here, we report on a 32-year-old female lung adenocarcinoma patient with positive PD-L1 and negative driver gene detected by DNA-based next-generation sequencing (NGS). A radical resection of the primary lesion after chemotherapy combined with PD-1 checkpoint inhibitor administration indicated primary immuno-resistance according to her pathological response and rapid relapse. A rare was detected by RNA-based NGS, which was confirmed by fluorescence hybridization. Multiplex immunofluorescence revealed a PD-L1 related heterogeneous immunosuppressive microenvironment with little distribution of CD4+ T cells and CD8+ T cells. Savolitinib therapy resulted in a progression-free survival (PFS) of >12 months, until a new secondary resistance mutation in p.D1228H was detected by re-biopsy and joint DNA-RNA-based NGS after disease progression. In this case, fusion NSCLC was primarily resistant to immunotherapy, sensitive to savolitinib, and developed secondary p.D1228H mutation after targeted treatment. DNA-RNA-based NGS is useful in the detection of such molecular events and tracking of secondary mutations in drug resistance. To this end, DNA-RNA-based NGS may be of better value in guiding precise diagnosis and individualized treatment in this patient population.