Blood cell count indexes as predictors of outcomes in advanced non-small-cell lung cancer patients treated with Nivolumab

Abstract

Lung cancer is the most common malignancy worldwide. Despite significant advances in diagnosis and treatment, mortality rates remain extremely high, close to incidence rates. Several targeted therapies have been recently introduced for the treatment of non-small cell lung cancer (NSCLC), the most common type of lung cancer. Nivolumab, a monoclonal antibody that targets programmed death-1 (PD-1), was the first immune checkpoint inhibitor approved for the treatment of patients with advanced/metastatic NSCLC not responding to platinum-based chemotherapy. Biomarkers predicting response to these therapies would allow early identification of non-responders and timely implementation of appropriate combination strategies, avoiding inadequate and expensive therapies. The role of the neutrophil to lymphocyte ratio and other blood cell count indexes as possible biomarkers of response has been recently investigated. We discuss the encouraging results reported on the topic, provide new data from our personal experience, and discuss opportunities for further research.

EPSILoN: A Prognostic Score for Immunotherapy in Advanced Non-Small-Cell Lung Cancer: A Validation Cohort

“…The identification of prognostic and/or predictive biomarkers in order to recognize potential responders to anti-PD-1/PD-L1 inhibitors is deeply needed. The early identification of nonresponders could avoid inadequate treatments, unnecessary toxicity and high costs [18]. According to clinical factors, there is no agreement on the advantage of ICIs in a specific clinical subcategory of patients.…”

“…Immunotherapy-related survival outcomes correlated with type of metastases at baseline ICIs are unknown. However, some studies revealed that ICI efficacy varies based on different metastatic sites [18,29]. This organ-specific response may be the result of the different PD-L1 expression, microenvironment and genetic heterogeneity profiles between primary and metastatic sites.…”

“…The evaluation of different biomarkers in a single prognostic score rather than focusing on a single biomarker permits to better identify patients who most likely will (or will not) benefit from ICIs [13]. Many immune-based prognostic scores were studied using clinical features and blood biomarkers such as lung immune prognostic index (LIPI) [50], advanced lung cancer inflammation index (ALI) [59], immunotherapy sex-ECOG-NLR-delta NLR (iSEND) [60], systemic inflammation index (SII) [18,61] and aggregate index of systemic inflammation (AISI) [61]. All these scores incorporated NLR and most of them included ECOG PS and LDH.…”

“…The LIPI score from Mezquita et al was the only one with a validation set of patients treated with ICIs and a control cohort of patients treated with chemotherapy alone in the same setting [50]. Moreover, some of the reported scores were not associated with survival at baseline [50,59,61] but only at time-series analysis (i.e., at 6 weeks of treatment) [18].…”

Turning cold tumors into hot tumors: harnessing the potential of tumor immunity using nanoparticles

“…In the light of the critical importance of innate immunity against cancer, one can assume that affecting lymphocytes count or other cells implicated in the immune response will have deleterious effects on the clinical outcome first, and will impair the efficacy of any immunotherapy-based strategy next, thus triggering innate resistance. For instance, several studies have suggested that elevated neutrophil-to-lymphocyte ratios (i.e., NLR >5) or diminished absolute lymphocyte count are associated with poor clinical outcome in patients treated with immune check point inhibitors [15,16].…”