The CALLY Index Is Associated with Overall Survival in Patients with De Novo Metastatic Gastric Adenocarcinoma

Background and Objectives: Systemic inflammation, nutritional impairment, and immune dysregulation are important determinants of outcomes in advanced malignancies. The C-reactive protein–albumin–lymphocyte (CALLY) index is a composite biomarker that reflects these biological domains, but its prognostic relevance in de novo metastatic gastric adenocarcinoma has not been well defined. Materials and Methods: This multicenter retrospective cohort study included 234 patients with de novo metastatic gastric adenocarcinoma treated between January 2015 and December 2025. Baseline CALLY was calculated before systemic treatment. A cohort-specific CALLY threshold of 1.21 was obtained using conventional ROC analysis, with all-cause mortality status at last follow-up as the binary outcome. Survival was evaluated using Kaplan–Meier analysis and Cox proportional hazards regression. To avoid guarantee-time bias, treatment exposure variables that became known only after treatment initiation, including the number of chemotherapy cycles delivered, were excluded from the baseline Cox models. Diagnosis period was included in the multivariable model to account for treatment-era heterogeneity. Results: Overall, 133 patients (56.8%) were classified as low-CALLY and 101 (43.2%) as high-CALLY. Median OS was significantly longer in the high-CALLY group than in the low-CALLY group (13.9 vs. 8.6 months; log-rank p < 0.001). Low CALLY was associated with inferior OS in univariable analysis (HR: 1.77, 95% CI: 1.31–2.38; p < 0.001) and remained associated with worse OS after adjustment for baseline clinicopathological factors, first-line treatment category, and diagnosis period (adjusted HR: 1.77, 95% CI: 1.24–2.53; p = 0.002). The PFS difference between the CALLY groups was not statistically significant (HR: 1.15, 95% CI: 0.87–1.51; p = 0.326). Conclusions: Low baseline CALLY was independently associated with shorter OS in this retrospective cohort. These findings support CALLY as a practical candidate prognostic biomarker, while external validation and time-to-event-based cut-off assessment are needed before clinical implementation.