Exome-Based Genomic Markers Could Improve Prediction of Checkpoint Inhibitor Efficacy Independently of Tumor Type.
Lorraine DalensJulie LecuelleLaure FavierCléa FraisseAurélie LagrangeCourèche KaderbhaiRomain BoidotSandy ChevrierHugo MananetValentin DerangèreCaroline TruntzerFrançois GhiringhelliPublished in: International journal of molecular sciences (2023)
Immune checkpoint inhibitors (ICIs) have improved the care of patients in multiple cancer types. However, PD-L1 status, high Tumor Mutational Burden (TMB), and mismatch repair deficiency are the only validated biomarkers of efficacy for ICIs. These markers remain imperfect, and new predictive markers represent an unmet medical need. Whole-exome sequencing was carried out on 154 metastatic or locally advanced cancers from different tumor types treated by immunotherapy. Clinical and genomic features were investigated using Cox regression models to explore their capacity to predict progression-free survival (PFS). The cohort was split into training and validation sets to assess validity of observations. Two predictive models were estimated using clinical and exome-derived variables, respectively. Stage at diagnosis, surgery before immunotherapy, number of lines before immunotherapy, pleuroperitoneal, bone or lung metastasis, and immune-related toxicity were selected to generate a clinical score. KRAS mutations, TMB, TCR clonality, and Shannon entropy were retained to generate an exome-derived score. The addition of the exome-derived score improved the prediction of prognosis compared with the clinical score alone. Exome-derived variables could be used to predict responses to ICI independently of tumor type and might be of value in improving patient selection for ICI therapy.
Keyphrases
- copy number
- healthcare
- squamous cell carcinoma
- free survival
- end stage renal disease
- locally advanced
- chronic kidney disease
- small cell lung cancer
- palliative care
- cell cycle
- case report
- radiation therapy
- stem cells
- bone mineral density
- peritoneal dialysis
- cell proliferation
- atrial fibrillation
- lymph node metastasis
- gene expression
- young adults
- percutaneous coronary intervention
- health insurance
- pain management