Pulmonary function test (PFT) and circulating biomarkers in immune-related pneumonitis (irP) in advanced non-small cell lung cancer (aNSCLC): A real-world multidisciplinary experience

BackgroundThe role of immune checkpoint inhibitors (ICIs) in NSCLC is well established and it is associated with improvement in survival and quality of life. The early detection, multidisciplinary management and proper follow-up of immune-related adverse events (irAEs) is one of the key issues for further improving diagnostic therapeutic pathways, while irP still represents a major cause for serious AE.MethodsWe retrospectively collected clinicopathological data of patients (pts) consecutively treated with ICIs at our Institution. Data about outcomes, irAE management and blood test values were collected. Data were matched with Pneumology database and PFT performed before the start of ICIs (≤40 days) were recorded. Primary endpoint was to investigate the role of PFT assessed at baseline in predicting the risk for irP.Results480 aNSCLC pts treated with ICIs were included: 161 had available basal PFT and were considered for the current interim analysis. After a median follow-up of 8.2 months, 73 (45%) pts experienced any irAE, 13 (8%) experienced irP: higher grade was 1-2 in 10 cases, and 3 in 3 cases. Median time to irP onset was 24 weeks. IrP caused hospitalization in 3 cases and permanent of ICI discontinuation in 10. The onset of irP was associated with longer progression-free survival (p=0.03) and overall survival (p= 0.01). No clinicopathological feature such as smoking status and previous thoracic radiotherapy was associated with a higher risk of irP. Low baseline neutrophil count was associated with an increased risk of irP (OR 1.51, 95% CI 1.13-2.17, p=0.011). Among PFT parameters, a reduced Tiffeneau index was significantly associated with an increased probability of developing irP (OR 1.04, 95% CI 1.00-1.09, p=0.041), even in the absence of a previous diagnosis of chronic obstructive pulmonary disease. Predictors were confirmed through logistic regression multivariate analysis.ConclusionsPFT performed before ICIs is able to predict the risk of irP and represents a simple, cost-effective tool for personalizing follow-up of pts receiving ICIs, thus confirming the role of multidisciplinary approach of irAEs. Prospective validation has been planned.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureG. Pasello: Financial Interests, Personal, Invited Speaker: Amgen, Eli Lilly, Novartis, MSD, Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Janssen; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Other, unconditioned support: AstraZeneca, MSD; Non-Financial Interests, Principal Investigator: AstraZeneca, Roche, Novartis, Lilly, Janssen, Pharmamar. V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, GSK, AstraZeneca, Gilead, Exact Sciences; Financial Interests, Personal, Advisory Board: Eli Lilly, Novartis, MSD, Gilead, Eli Lilly, Merck Serono, Exact Sciences, Eisai, Olema Oncology, AstraZeneca, Daiichi Sankyo, Pfizer; Financial Interests, Institutional, Local PI: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck, GSK, Daiichi Sankyo, Nerviano, Pfizer; Non-Financial Interests, Member: ASCO. L. Bonanno: Financial Interests, Institutional, Advisory Board: AstraZeneca, MSD, BMS, Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca, MSD, BMS, Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Institutional, Steering Committee Member: AstraZeneca; Non-Financial Interests, Principal Investigator: Roche, AstraZeneca, Boehringer Ing, MSD, BMS, Janssen, PharMamar, Arcus Biosciences. All other authors have declared no conflicts of interest.