Clinically relevant prognostic and predictive markers for immune-checkpoint-inhibitor (ICI) therapy in non-small cell lu

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Clinically relevant prognostic and predictive markers for immune-checkpoint-inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC) Wolfgang M. Brueckl1,2* , Joachim H. Ficker1,2 and Gloria Zeitler2

Abstract Background: Immune checkpoint inhibitors (ICI) either alone or in combination with chemotherapy have expanded our choice of agents for the palliative treatment of non-small cell lung cancer (NSCLC) patients. Unfortunately, not all patients will experience favorable response to treatment with ICI and may even suffer from severe side effects. Therefore, prognostic and predictive markers, beyond programmed death ligand 1 (PD-L1) expression status, are of utmost importance for decision making in the palliative treatment. This review focuses on clinical, laboratory and genetic markers, most of them easily to obtain in the daily clinical practice. Results: Recently, a number of prognostic and predictive factors in association to palliative ICI therapy have been described in NSCLC. Besides biometric parameters and clinical characteristics of the tumor, there are useful markers from routine blood sampling as well as innovative soluble genetic markers which can be determined before and during ICI treatment. Additionally, the level of evidence is noted. Conclusions: These factors can be helpful to predict patients’ outcome and tumor response to ICI. They should be implemented prospectively in ICI based clinical trials to develop reliable algorithms for palliative NSCLC treatment. Keywords: Immunotherapy, Immune checkpoint inhibitor (ICI), PD-L1 inhibitor, NSCLC, Prognostic, Predictive, Biomarker

* Correspondence: [email protected] 1 Department of Respiratory Medicine, Allergology and Sleep Medicine / Nuremberg Lung Cancer Center, Paracelsus Medical University, General Hospital Nuremberg, Prof.-Ernst-Nathan-Str. 1, 90419 Nuremberg, Germany 2 Paracelsus Medical Private University Nuremberg, Prof.-Ernst-Nathan-Str. 1, 90419 Nuremberg, Germany © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise state