An exploratory ImmunoScore based on early on-treatment changes in NLR and LDH in small-cell lung cancer receiving first-line chemoimmunotherapy

BACKGROUND: Early monitoring biomarkers for first-line chemoimmunotherapy in extensive-stage small-cell lung cancer (SCLC) remain limited. Dynamic blood-based changes may better reflect treatment-related alterations than static baseline values. METHODS: We conducted a retrospective multicenter study comprising a 225-patient baseline cohort, a 148-patient dynamic development cohort of chemoimmunotherapy-treated patients with paired baseline/post-cycle 2 blood tests, and a 49-patient independent external validation cohort. Early relative changes in routine blood-based markers were analyzed for associations with objective response rate (ORR) and survival. A simplified ImmunoScore based on standardized changes in neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) was developed and externally validated. RESULTS: Elevated baseline NLR, platelet-to-lymphocyte ratio (PLR), LDH, and D-dimer were associated with shorter overall survival (OS), whereas only LDH remained independently prognostic. In the development cohort, ΔNLR showed the strongest association with ORR, and both ΔNLR and ΔLDH were associated with progression-free survival (PFS). The ImmunoScore achieved areas under the curve (AUCs) of 0.895 and 0.938 for ORR prediction in the development and external validation cohorts. CONCLUSIONS: The ImmunoScore may provide an interpretable post-cycle 2 framework for ORR prediction and subsequent survival stratification in SCLC. Given the small external validation cohort, these findings remain exploratory and require prospective multicenter validation.