Influence of DNA Mismatch Repair (MMR) System in Survival and Response to Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC): Retrospective Analysis
Alejandro Olivares-Hernández,
Edel del Barco Morillo,
Carmen Parra Pérez,
José Pablo Miramontes-González,
Luis Figuero-Pérez,
Teresa Martín-Gómez,
Roberto Escala-Cornejo,
Lorena Bellido Hernández,
Rogelio González Sarmiento,
Juan Jesús Cruz-Hernández,
María Dolores Ludeña de la Cruz
Affiliations
Alejandro Olivares-Hernández
Department of Medical Oncology, University Hospital of Salamanca, 37007 Salamanca, Spain
Edel del Barco Morillo
Department of Medical Oncology, University Hospital of Salamanca, 37007 Salamanca, Spain
Carmen Parra Pérez
Department of Medicine, University of Salamanca, 37007 Salamanca, Spain
José Pablo Miramontes-González
Department of Internal Medicine, University Hospital Rio Hortega, 47012 Valladolid, Spain
Luis Figuero-Pérez
Department of Medical Oncology, University Hospital of Salamanca, 37007 Salamanca, Spain
Teresa Martín-Gómez
Department of Medical Oncology, University Hospital of Salamanca, 37007 Salamanca, Spain
Roberto Escala-Cornejo
Instituto de Investigación Nacional (SOLCA) de Guayaquil, Guayaquil 090514, Ecuador
Lorena Bellido Hernández
Department of Medical Oncology, University Hospital of Salamanca, 37007 Salamanca, Spain
Rogelio González Sarmiento
Institute for Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain
Juan Jesús Cruz-Hernández
Department of Medical Oncology, University Hospital of Salamanca, 37007 Salamanca, Spain
María Dolores Ludeña de la Cruz
Department of Medicine, University of Salamanca, 37007 Salamanca, Spain
Mutations in the mismatch repair (MMR) system predict the response to immune checkpoint inhibitors (ICIs) like colon or gastric cancer. However, the MMR system’s involvement in non-small cell lung cancer (NSCLC) remains unknown. Addressing this issue will improve clinical guidelines in the case of mutations in the main genes of the MMR system (MLH1, MSH2, MSH6, and PMS2). This work retrospectively assessed the role that these gene mutations play in the response to and survival of ICIs in NSCLC. Patients with NSCLC treated with nivolumab as the second-line treatment in the University Hospital of Salamanca were enrolled in this study. Survival and response analyses were performed according to groups of MMR system gene expression (MMR expression present or deficiency) and other subgroups, such as toxicity. There was a statistically significant relationship between the best response obtained and the expression of the MMR system (p = 0.045). The presence of toxicity grade ≥ 3 was associated with the deficiency expression of MMR (dMMR/MSI-H) group (p = 0.022; odds ratio = 10.167, 95% confidence interval (CI) 1.669–61.919). A trend towards greater survival and response to ICIs was observed in NSCLC and dMMR. Assessing the genes in the MMR system involved in NSCLC is key to obtaining personalized immunotherapy treatments.
