Serum cytokines predict efficacy and toxicity, but are not useful for disease monitoring in lung cancer treated with PD-(L)1 inhibitors.

PD-(L)1 inhibitors (IO) have improved the prognosis of non-small-cell lung cancer (NSCLC), but more reliable predictors of efficacy and immune-related adverse events (irAE) are urgently needed. Cytokines are important effector molecules of the immune system, whose potential clinical utility as biomarkers remains unclear. Serum samples from patients with advanced NSCLC receiving IO either alone in the first (1L, n=46) and subsequent lines (n=50), or combined with chemotherapy (ICT, n=108) were analyzed along with age-matched healthy controls (n=15) at baseline, after 1 and 4 therapy cycles, and at disease progression (PD). Patients were stratified in rapid progressors (RP, progression-free survival [PFS] <120 days), and long-term responders (LR, PFS >200 days). Cytometric bead arrays were used for high-throughput quantification of 20 cytokines and other promising serum markers based on extensive search of the current literature. Untreated NSCLC patients had increased levels of various cytokines and chemokines, like IL-6, IL-8, IL-10, CCL5, G-CSF, ICAM-1, TNF-RI and VEGF (fold change [FC]=1.4-261, p=0.026-9x10 Untreated NSCLC is characterized by increased blood levels of several pro-inflammatory and angiogenic effectors, which decrease under ICT. Baseline serum cytokine levels could be exploited for improved prediction of subsequent IO benefit (in particular TNF-RI) and development of irAE (

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Copyright © 2022 Schindler, Lusky, Daniello, Elshiaty, Gaissmaier, Benesova, Souto-Carneiro, Angeles, Janke, Eichhorn, Kazdal, Schneider, Liersch, Klemm, Schnitzler, Stenzinger, Sültmann, Thomas and Christopoulos.

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Author KB received consultancy and/or speaker fees and/or travel reimbursements from Abbvie, Bristol Myers Squibb BMS, Gilead/Galapagos, Janssen, Merck Sharp & Dohme MSD, Mundipharma, Novartis, Pfizer, Roche, Viatris, UCB, as well as scientific support from the Medical Faculty of University of Heidelberg, Rheumaliga Baden-Württemberg e.V., AbbVie, and Novartis. Author FE received personal fees from Roche and BMS; DK: advisory board and speaker’s honoraria from AstraZeneca, BMS, Pfizer. Author AS received advisory board honoraria from BMS, AstraZeneca, ThermoFisher, Novartis, speaker’s honoraria from BMS, Illumina, AstraZeneca, Novartis, ThermoFisher, MSD, Roche, and research funding from Chugai. Author HoS received research grants and personal fees from Roche Sequencing Solutions, outside the submitted work. Author MT received advisory board honoraria from Novartis, Lilly, BMS, MSD, Roche, Celgene, Takeda, AbbVie, Boehringer, speaker’s honoraria from Lilly, MSD, Takeda, research funding from AstraZeneca, BMS, Celgene, Novartis, Roche and travel grants from BMS, MSD, Novartis, Boehringer. Author PC received research funding from Amgen, AstraZeneca, Merck, Novartis, Roche, Takeda, and advisory board/lecture fees from AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Gilead, Novartis, Pfizer, Roche, Takeda. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.