1. The Pan-Immune-Inflammation Value in microsatellite instability–high metastatic colorectal cancer patients treated with immune checkpoint inhibitors
- Author
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Giovanni Fucà, Margherita Ambrosini, Rossana Intini, Maria Antista, Matteo Fassan, Giuseppe Curigliano, Alessandra Anna Prete, Marta Brambilla, Andrea Spallanzani, Federica Morano, Massimiliano Salati, Carmen Belli, Filippo Pietrantonio, Elisabetta Fenocchio, Beatrice Borelli, Sara Lonardi, Vittorina Zagonel, Francesca Corti, Filippo de Braud, and Virginia Quarà
- Subjects
Blood Platelets ,Male ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Time Factors ,Neutrophils ,Colorectal cancer ,Immune checkpoint inhibitors ,Lymphocyte ,Monocytes ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,0302 clinical medicine ,Antigen ,Internal medicine ,Tumor Microenvironment ,Humans ,Medicine ,Genetic Predisposition to Disease ,Neoplasm Metastasis ,Pan-Immune-Inflammation Value ,Immune Checkpoint Inhibitors ,Aged ,Retrospective Studies ,Inflammation ,business.industry ,Microsatellite instability ,medicine.disease ,Progression-Free Survival ,Phenotype ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Absolute neutrophil count ,Biomarker (medicine) ,Biomarkers ,Deficient mismatch repair ,Female ,Microsatellite Instability ,Colorectal Neoplasms ,business ,Immune inflammation - Abstract
Immune checkpoint inhibitors (ICIs) yielded unprecedented efficacy in patients with microsatellite instability (MSI)-high metastatic colorectal cancer (mCRC). Since the Pan-Immune-Inflammation Value (PIV) is a blood-based biomarker with prognostic usefulness in mCRC, it might predict clinical outcomes and primary resistance to ICIs.We retrospectively analysed the association of PIV and its early modulation at 3/4 weeks after treatment initiation with the outcomes of MSI-high mCRC patients receiving anti-programmed death-(ligand)1 (PD-[L]1) +/- anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) agents. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. PIV cut-offs were determined using the maximally selected rank statistics.A total of 163 patients were included. In the multivariable models for overall survival (OS) and progression-free survival (PFS), both high (492) baseline PIV (OS: adjusted [a] HR, 3.00; 95% CI, 1.49-6.04, p = 0.002; PFS: aHR, 1.91; 95% CI, 1.06-3.44, p = 0.031) and early PIV increase ≥+30% (OS: aHR, 3.21; 95% CI, 1.65-6.23, p 0.001; PFS: aHR, 2.25; 95% CI, 1.30-3.89, p = 0.003) confirmed an independent prognostic impact. After stratifying patients according to baseline PIV and ICI regimen, OS and PFS were significantly worse in subjects with high PIV receiving anti-PD-1/PD-L1 monotherapy. Early PIV increase was an independent predictor of clinical benefit (aOR, 0.23; 95% CI, 0.08-0.66; p = 0.007), whereas a trend was observed for baseline PIV (aOR, 0.33; 95% CI, 0.10-1.07; p = 0.065).PIV is a strong predictor of outcomes in MSI-high mCRC patients receiving ICIs. Prospective validation of these results is required to establish its role as a stratification factor for personalised combination strategies.
- Published
- 2021