TY - JOUR T1 - High levels of chromosomal aberrations negatively associate with benefit to checkpoint inhibition in NSCLC JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2021-004197 VL - 10 IS - 4 SP - e004197 AU - Joan Frigola AU - Caterina Carbonell AU - Patricia Iranzo AU - Nuria Pardo AU - Ana Callejo AU - Susana Cedres AU - Alex Martinez-Marti AU - Alejandro Navarro AU - Mireia Soleda AU - Jose Jimenez AU - Javier Hernandez-Losa AU - Ana Vivancos AU - Enriqueta Felip AU - Ramon Amat Y1 - 2022/04/01 UR - http://jitc.bmj.com/content/10/4/e004197.abstract N2 - Background Immune checkpoint inhibitors (ICIs) targeting the programmed cell death 1/programmed death-ligand 1 axis have transformed the management of advanced non-small cell lung cancer (NSCLC). However, many patients do not benefit from this type of treatment, and thus several molecular biomarkers of benefit have been explored. The value of somatic copy number alterations (SCNAs) burden remains elusive.Patients and methods We assembled a cohort of 109 patients with NSCLC treated with ICIs and available tumor samples. We performed shallow whole-genome sequencing on 89 patients to determine genome-wide SCNAs and targeted gene expression analysis on 63 patients to study immune infiltration. We analyzed SCNAs burden in different ways (ie, the fraction of the genome altered or number of events) and studied their association with ICIs benefit based on survival analysis. We correlated SCNAs burden and immune infiltration on 35 patients of our cohort and on patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA).Results High SCNAs burden, computed in diverse ways, is negatively associated with ICIs progression-free survival (PFS), with the fraction of the genome altered (FGA) by arm and chromosome events showing the strongest association with PFS (p=0.002) (n=77). Nevertheless, we found differences in SCNAs across some clinicopathological features (sample site origin). A multivariate analysis adjusted for relevant characteristics showed that the FGA of arm and chromosome alterations was strongly associated with PFS (HR=2.21, p=3.3 x 10−5). Finally, we confirmed that SCNAs burden negatively correlates with tumor immune infiltration (n=35), although this correlation was not found for the males studied. Similar results were observed in the TCGA cohort.Conclusions SCNAs burden is a potential biomarker of benefit to ICIs in patients with NSCLC, although there appear to be some nuances worth consideration. Further studies will be needed to establish its role as a biomarker of benefit to ICIs.All data relevant to the study are included in the article or uploaded as supplementary information. SCNAs and gene expression data will be available upon request. ER -