Prognostic value of early NLR normalization in MSI-H mCRC: A real-world analysis.

Abstract

e15625 Background: Immune Checkpoint Inhibitors (ICIs) are the standard of care first line for Microsatellite Instability-High (MSI-H) metastatic colorectal cancer (mCRC). Baseline Neutrophil Lymphocyte Ratio (NLR) and Absolute Lymphocyte Count (ALC) have been proposed as prognostic markers for ICI response across solid tumors. However, it remains unclear if early kinetic/dynamic changes in the NLR affect the long term survival outcomes. We evaluated whether early NLR kinetics predict Overall Survival (OS) independent of baseline nutritional status. Methods: We used the TriNetX global network database to identify patients with metastatic colorectal cancer treated with first line ICI therapy. To strictly isolate the MSI-High population, we excluded any patient who received cytotoxic chemotherapy within one year prior to or one month after the index date. We stratified patients into two cohorts based on inflammatory kinetics during the first 3–10 weeks of treatment: Responders (High Baseline NLR normalized to < 5) and Non-Responders (High Baseline NLR remained > 5). We used 1:1 Propensity Score Matching to balance key characteristics, including age, sex, steroid use, and baseline nutritional status (albumin). Results: A total of 768 propensity matched patients were analyzed (384 per cohort). Baseline characteristics were well balanced, including serum albumin (P = 0.07), which suggests comparable nutritional status. Early NLR normalization was associated with a significantly superior Median Overall Survival of 43 months compared to 21 months for Non-Responders. This survival benefit persisted over a decade, with 5-year and 10-year survival rates of 46.7% and 34.8% for Responders, compared to 30.1% and 18.4% for Non-Responders (HR 0.59; P < 0.001). Time to Next Treatment did not differ significantly between groups. Conclusions: Our study provides compelling real world evidence that early improvement in systemic inflammation as reflected by NLR normalization, is a critical determinant of long-term survival in patients with MSI-H mCRC receiving first-line ICI. Importantly, this survival benefit is durable and independent of baseline nutritional status. These findings validate NLR kinetics as a robust, cost effective biomarker for early evidence of therapeutic efficacy. Overall survival and hazard ratio (responders vs non-responders). Outcome Measure Responders (NLR > 5 → ≤ 5) Non-Responders (NLR > 5 → > 5) HR (95% CI) P-Value N (Propensity Matched) 384 384 Median Overall Survival 43 Months 21 Months 0.59 (0.47–0.74) <0.001 5-Year Survival Rate 46.70% 30.10% 0.584 (0.467–0.731) <0.001 10-Year Survival Rate 34.80% 18.40% 0.592 (0.474–0.738) <0.001 Abbreviations: HR, Hazard Ratio; NLR, Neutrophil-to-Lymphocyte Ratio; CI, Confidence Interval.