Potential predictors of immunotherapy-induced pneumonitis in non-small cell lung cancer (NSCLC)

<bold>Background:</bold> Immunotherapy (IT) represents the therapeutic frontier in non-oncogene addicted NSCLC. Immune-related adverse events (irAEs) are generally manageable but need early recognition and proper management to avoid severe outcomes. Clinical and molecular predictors for irAEs are under investigation. <bold>Aim:</bold> To identify potential predictors of IT-induced pneumonitis (ITP) among clinical, functional and lab data in a cohort of NSCLC patients (pts). <bold>Methods:</bold> Data of 480 IT-treated pts were systematically reviewed. Among these, 31 pts w/o toxicity, 30 with ITP and 20 with toxicities other than ITP (OT) were compared in preliminary analysis. <bold>Results:</bold> Age, gender and smoke exposure did not differ in the 3 groups (overall, 69土10 y/o, males: 64%, smokers: 89%, 38土26 pack years). The Tiffeneau index, measured before starting IT, was below 70% in ITP pts 68(62-74)%, lower than pts w/o toxicities and OT 77(68-83)%; p=0.04. The neutrophil (N) count was reduced in ITP compared to pts w/o irAE [3.5(2.4-5.1)vs 5.4(2.8-6.9)x10.9/L; p=0.03)] and showed a trend vs OT 6(4.4-9.1)x10.9/L; p=0.07. Pts with pre-IT N count <5.35x10.9/L had higher risk of ITP (RR 2.25). Having pre-IT blood N <5.35x10.9/L and fixed airflow limitation accurately identified ITP pts (sensitivity 83%, specificity 77%). Patients w/o toxicities had a higher neutrophil to lymphocyte ratio than those who developed ITP or OT (p=0.03) and reduced survival at follow-up (HR 2.7 CI 1.3-5.7; p=0.0008). <bold>Conclusions:</bold> Preliminary data suggests a role for pre-IT spirometry and blood count in predicting the risk for irAES. Whether COPD and low blood neutrophils are red flags for ITP will be confirmed by additional analyses ongoing in the whole cohort.