AUTHOR=Dong Wen , Lei Pengfei , Liu Xin , Li Qin , Cheng Xiangyang 

TITLE=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

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.686057

DOI=10.3389/fimmu.2021.686057

ISSN=1664-3224

ABSTRACT=<p>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 (<italic>ALK</italic>) gene rearrangement rarely benefit from PD-L1 inhibitors. Besides the secondary mutations in <italic>ALK</italic> 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 <italic>EML4-ALK</italic> gene rearrangement and <italic>BRAF</italic> 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 <italic>ALK</italic> gene rearrangement.</p>