Abstract 1074P
Background
Single agent immunotherapy (IO) has been accepted as standard frontline treatment for NSCLC with high PD-L1 expression, however most of the patients do not respond and some of them could benefit from chemo-immunotherapy (CT+IT). Low-density neutrophils (LDNs) are cells with immunosuppresive activities enriched in peripheral blood of cancer patients. We have studied the association between baseline LDNs and response to IO in NSCLC.
Methods
PBMCs from 31 patients treated with IO and 21 treated with CT + IT were purified from fresh peripheral blood. Baseline LDNs were quantified through flow cytometry, and the proportions were correlated with clinical outcomes. Plasma from patients was compared through quantitative proteomics.
Results
Elevated baseline LDNs predict primary resistance to IO monotherapy. ROC analysis established a threshold of 7.09% (AUC 0.895), over which ORR was 0% and mPFS of 6.1 wk. No association was found between LDN levels and resistance to CT+IT (AUC 0.471), with an ORR of 57.1% when LDNs were > 7.09% and mPFS not reached (NR). A depletion of LDNs was observed in patients who responded to CT + IT. Ex vivo cocultures demonstrated that soluble factors present in plasma from high LDN patients prevented anticancer cytotoxicity. Comparative quantitative proteomics revealed the key role of the HGF/c-MET pathway.
Conclusions
High baseline LDN levels are associated with primary resistance to IO monotherapy in patients with NSCLC. However, these patients can respond to CT+IT, thus identifying a subgroup whom should be offered this treatment regardless of high PD-L1 tumor expression. The upregulation of HGF/c-MET suggests that that targeting this pathway could have synergistic effect.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The authors are supported and funded by the Spanish Association against Cancer (AECC, PROYE16001ESCO), Instituto de Salud Carlos III (ISCIII-FEDER, FIS. PI17/02119), and a Biomedicine Project grant from the Department of Health of the Government of Navarre (BMED 050-2019). H.A. is supported by the Clínico Junior 2019 scholarship from the AECC (CLJUN19010ARAS). D.E. is funded by a Miguel Servet Fellowship (ISC III, CP12/03114, Spain).
Disclosure
H. Arasanz: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Principal Investigator: Ferrer Farma. R. Vera: Financial Interests, Personal, Advisory Board: Amgen, Bayer, AstraZeneca, Merck, Roche, Sanofi, MSD, Lilly, Servier, Novartis. All other authors have declared no conflicts of interest.