4692 - Immune cell biomarkers on neo-adjuvant chemo-immunotherapy treatment for resectable stage IIIA NSCLC patients

Background

Immunotherapy has become the main therapy in advanced NSCLC patients, but recently, combination with chemotherapy in locally advanced stages is showing promising results. Many studies have described peripheral blood immune cells parameters as response biomarkers. In our study, we described the effect of neo-adjuvant chemo-immunotherapy treatment in Complete Blood Count (CBC) and Peripheral blood mononuclear cells phenotype, as well as, the association of these parameters with pathological response.

Methods

46 resectable stage IIIA NSCLC patients treated with neo-adjuvant chemo-immunotherapy from NADIM clinical trial were analysed. Samples were extracted before initiating the neo-adjuvant treatment with nivolumab plus carboplatin and at the third cycle before patients underwent surgery. We classified patients in 3 subgroups of pathological response: complete (pCR), mayor (<10% viable tumour) and incomplete (>10% viable tumour, pIR).

Results

Absolute numbers of Leucocytes, Eosinophil, Monocytes, Neutrophils, Haemoglobin and Platelets from hemograms were significantly reduced after treatment. However, no changes were observed for Lymphocytes, Basophils, LDH levels or the lung immune prognostic index (LIPI). Additionally, post-treatment neutrophil-to-lymphocyte (NLR), myeloid-to-lymphoid lineage (M:L) and platelets-to-lymphocytes (PLR) ratios were decreased. Remarkably, from all the CBC absolute numbers and ratios, only PLR variation showed differences between pCR and pIR. On the other hand, percentages of T cells, B cells, NK cells and macrophages did not vary after treatment, however activation of CD4 T cells and NK cells were significantly downregulated after treatment, associated to pCR. Also, PD-1 expression on T and NK cells pre-treatment was higher on pCR compared to pIR, reaching statistical significance only on CD4 T cells.

Conclusions

In our study, we described predictive biomarkers of response to treatment. A higher decrease on PLR post-treatment is associated to pIR. Moreover, higher expression of PD-1 pre-treatment in CD4 T cells, as well, as a reduced activation on CD4 T cells and NK cells, after treatment are associated to pCR.

Clinical trial identification

NCT 03081689; EudraCT 2016-003732-20.

Editorial acknowledgement

Legal entity responsible for the study

Spanish Lung Cancer Group.

Funding

BMS.

Disclosure

M. Provencio: Advisory / Consultancy: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Boehringer. All other authors have declared no conflicts of interest.