Monocyte-Platelet-Hemoglobin-Hematocrit score and the role of hematological parameters in predicting treatment response to immune checkpoint inhibitors and survival outcomes in non-small cell lung cancer patients-a retrospective study.

Background: Lung cancer is the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) representing 85% of cases. Immune checkpoint inhibitors (ICIs) have improved NSCLC treatment, but many patients still have poor responses or severe side effects. Reliable biomarkers are needed to predict treatment outcomes and personalize therapy. Hematological markers from complete blood count (CBC) have gained attention as accessible, low-cost prognostic tools reflecting systemic inflammation and immune status. Most studies focus on baseline values, leaving the prognostic relevance of their dynamic changes during treatment underexplored. This highlights the importance of investigating longitudinal hematological profiles in immunotherapy settings. The aim of this study is to investigate whether longitudinal changes in CBC parameters can serve as prognostic biomarkers in NSCLC patients treated with ICI. Methods: This retrospective study included 141 patients with NSCLC treated with ICIs between 2018 and 2024 at Barretos Cancer Hospital, Brazil. Eligible patients were ≥18 years old, had a confirmed NSCLC diagnosis, and had documented advanced-stage disease. Clinical data, including demographics, Eastern Cooperative Oncology Group (ECOG) status, smoking history, tumor histology, programmed death ligand-1 (PD-L1) expression, CBC values, treatment regimen, and response assessments, were obtained from medical records. Hematological parameters were assessed at diagnosis, baseline, and after three cycles of ICI. These parameters were analyzed individually and through composite scores, including a novel Monocyte-Platelet-Hemoglobin-Hematocrit (MPHH) score. Response was evaluated by RECIST 1.1, and overall survival (OS) and progression-free survival (PFS) by Kaplan-Meier and Cox models. Results: The median age was 65 years, with adenocarcinoma representing the predominant histological subtype (57.1%). The majority of patients were diagnosed at stage IV (60.9%), and PD-L1 positivity was observed in 62.9% of cases. Overall, 70.5% of patients achieved a clinical response to immunotherapy. The MPHH score demonstrated significant prognostic value for both treatment response and survival outcomes. Non-responders exhibited higher baseline MPHH values (P=0.04). Lower baseline scores (≤400.3) were associated with improved OS (P=0.007) and PFS (P=0.01). Post-treatment assessments further supported its predictive role, as patients with MPHH ≤305.9 after three cycles of ICI therapy showed significantly longer overall (P=0.005) and PFS (P<0.001). Conclusions: These findings highlight the potential of CBC-derived scores, such as the MPHH, as valuable prognostic tools. CBC markers are particularly important in resource-limited settings where access to advanced molecular profiling is restricted. Integrating hematological profiles into clinical decision-making could facilitate more personalized treatment approaches and improve patient outcomes.