Characteristics and Hematological Indicators Predictors of Immunotherapy Response in Advanced Non-Small Cell Lung Cancer

Objective: Immune checkpoint inhibitors (ICIs) have significantly improved the treatment outcomes for advanced non-small cell lung cancer (NSCLC), but patient benefits vary individually. Therefore, identifying biomarkers to predict the efficacy and prognosis of immunotherapy is crucial. Hematological markers such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin-bilirubin (ALBI) score, and lactate dehydrogenase (LDH) levels may correlate with tumor prognosis. This study aimed to evaluate the prognostic value of these hematological and clinical markers in advanced NSCLC patients treated with ICIs, providing a basis for individualized treatment strategies. Methods: This retrospective study included NSCLC patients treated with ICIs at the Tumor Centers of Renmin Hospital of Wuhan University and Macheng City People’s Hospital between January 2021 and December 2023. Clinical data such as gender, age, ECOG PS score, clinical stage, and treatment details were collected. Patients were stratified based on NLR, PLR, LDH, and ALBI scores. ROC curve analysis assessed the predictive capacity of these markers for mortality risk. Chi-square tests, logistic regression, Kaplan-Meier survival analysis, and log-rank tests were used to analyze short-term efficacy, immune-related adverse events (irAEs), progression-free survival (PFS), and overall survival (OS). Cox regression identified independent prognostic factors for PFS and OS. Results: A total of 198 advanced NSCLC patients (median follow-up: 28.1 months) were included. Median PFS (mPFS) and OS (mOS) were 7.7 months (95% CI: 6.9~8.5) and 20.1 months (95% CI: 18.2~21.9), respectively. ROC analysis demonstrated significant predictive value for baseline NLR, PLR, ALBI, and LDH in mortality risk (AUC: 0.804, 0.694, 0.684, 0.726, respectively). Efficacy analysis revealed PD-L1 positivity (OR = 0.361, 95% CI: 0.161~0.808, P = 0.013) and ALBI < -2.68 (OR = 2.524, 95% CI: 1.148–5.552, P = 0.021) as independent predictors of objective response rate (ORR: 25.8%), while camrelizumab significantly reduced response rates (OR = 0.157, P = 0.006). In the squamous cell carcinoma subgroup, radiotherapy was an independent protective factor for tumor response (OR = 0.298, 95% CI: 0.094–0.95, P = 0.041). Baseline NLR, PLR, ALBI, and LDH significantly stratified PFS (P < 0.05): low NLR (8.7 vs. 7.1 months, P = 0.001), low PLR (7.9 vs. 7.4 months, P = 0.007), low ALBI (8.1 vs. 7.0 months, P = 0.028), and low LDH (9.5 vs. 7.1 months; 46.3% risk reduction, P < 0.001). In the adenocarcinoma subgroup, LDH remained an independent prognostic factor (9.5 vs. 6.8 months, P = 0.032). For squamous cell carcinoma, low NLR (9.1 vs. 7.1 months, P = 0.002), low PLR (10.2 vs. 7.4 months, P = 0.002), low ALBI (8.7 vs. 7.1 months, P = 0.022), and low LDH (9.1 vs. 7.5 months, P = 0.002) were significant. Baseline markers also predicted OS: low NLR (21.4 vs. 17.5 months, P < 0.001), low PLR (20.4 vs. 17.7 months, P = 0.009), and low LDH (21.4 months; 42.5% risk reduction, P < 0.001). Subtype analysis showed adenocarcinoma benefited from low NLR (21.4 vs. 16.5 months, P = 0.013) and low LDH (20.1 vs. 17.5 months, P = 0.021), while squamous carcinoma relied on low NLR (21.4 vs. 16.8 months, P = 0.008), low PLR (21.8 vs. 20.1 months, P = 0.024), low ALBI (21.4 vs. 18.2 months, P = 0.047), and low LDH (24.6 vs. 19.8 months, P = 0.001). Multivariate Cox analysis identified treatment response (SD/PD), radiotherapy, NLR, and LDH as independent predictors of PFS: SD (HR = 1.959) and PD (HR = 2.763) increased progression risk by 95.9% and 176.3% (P < 0.01), respectively; radiotherapy reduced risk by 29.2% (HR = 0.708, P = 0.041); NLR ≥ 3.72 (HR = 1.638) and LDH ≥ 226.5 U/L (HR = 1.783) increased risk by 63.8% and 78.3% (P < 0.05). For OS, adenocarcinoma (HR = 0.343) and squamous carcinoma (HR = 0.312) reduced mortality risk by 65.7% and 68.8% (P < 0.05), while SD (HR = 1.715), PD (HR = 2.536), NLR ≥ 3.72 (HR = 1.629), and LDH ≥ 226.5 U/L (HR = 1.826) increased risk by 71.5%, 153.6%, 62.9%, and 82.6% (P < 0.05). Baseline NLR and LDH correlated with irAEs risk: low NLR (55.4% vs. 37.1%, P = 0.010; OR = 1.976, 95% CI: 1.098~3.557, P = 0.023) and low LDH (62.2% vs. 35.3%, P < 0.001; OR = 2.881, 95% CI: 1.590~5.223, P < 0.001) increased irAEs incidence. Conclusions: Baseline hematological markers (NLR, PLR, ALBI, LDH) are valuable predictors of efficacy and prognosis in advanced NSCLC patients undergoing immunotherapy. Their prognostic roles vary by pathological subtype: squamous carcinoma relies more on inflammatory markers, while adenocarcinoma emphasizes metabolic markers and genetic mutations. This study provides a hematological biomarker-based stratification framework for individualized immunotherapy decisions in advanced NSCLC, offering critical guidance for optimizing treatment and prognosis management.