The Pan-Immune-Inflammation Value in microsatellite instability–high metastatic colorectal cancer patients treated with immune checkpoint inhibitors

• Published in: European journal of cancer (1990) Vol. 150; pp. 155 - 167
• Main Authors: Corti, Francesca, Lonardi, Sara, Intini, Rossana, Salati, Massimiliano, Fenocchio, Elisabetta, Belli, Carmen, Borelli, Beatrice, Brambilla, Marta, Prete, Alessandra A., Quarà, Virginia, Antista, Maria, Fassan, Matteo, Morano, Federica, Spallanzani, Andrea, Ambrosini, Margherita, Curigliano, Giuseppe, de Braud, Filippo, Zagonel, Vittorina, Fucà, Giovanni, Pietrantonio, Filippo
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2021; Elsevier Science Ltd
• Subjects: Antigens; Biomarkers; Cancer; Cell number; Colorectal cancer; Colorectal carcinoma; CTLA-4 protein; Cytotoxicity; Deficient mismatch repair; Immune checkpoint inhibitors; Inflammation; Inhibitors; Leukocytes (neutrophilic); Lymphocytes; Lymphocytes T; Metastases; Metastasis; Microsatellite instability; Monocytes; Pan-Immune-Inflammation Value; Patients; PD-1 protein; PD-L1 protein; Survival; PR; CBC; IHC; ICIs; Colorectal cancer; HR; Microsatellite instability; SD; Pan-Immune-Inflammation Value; mCRC; PD-L1; CTLA-4; PFS; dMMR; mm; a; i.e; MSI; OR; RECIST; OS; CI; TMB; Deficient mismatch repair; Immune checkpoint inhibitors; IQR; CR; ECOG PS; PD; NE; Biomarkers; PIV; PD-1; PCR
• ISSN: 0959-8049; 1879-0852; 1879-0852
• DOI: 10.1016/j.ejca.2021.03.043

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. •PIV is a composite immune-inflammation biomarker with prognostic usefulness in mCRC.•High baseline PIV identifies MSI-high mCRC patients with poorer outcomes upon ICIs.•Early PIV increase ≥+30% at 3/4 weeks independently correlates with poor OS and PFS.•Subjects with high PIV receiving anti-PD-1/PD-L1 monotherapy have worse OS and PFS.•Baseline PIV and early PIV variation correlate with primary ICIs resistance.