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

Abstract Background 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. Methods 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. Results 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  Conclusion 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.