Association between pre-treatment chest imaging and immune checkpoint inhibitor pneumonitis in lung cancer

SESSION TITLE: Lung Cancer Posters 6 SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/11/2023 12:00 pm - 12:45 pm PURPOSE: Immune checkpoint inhibitors (ICIs) are a first line and adjuvant treatment in advanced stage lung cancer. One of the main complications of ICI treatment is pneumonitis with an overall incidence of 2-5%; however, patient specific risk factors for developing ICI pneumonitis haven’t been well studied. We evaluated potential pre-treatment risk factors for ICI pneumonitis, including pre-treatment interstitial abnormalities on chest CT, previous cancer treatment, and pulmonary function testing (PFTs). METHODS: We conducted a retrospective cohort study of patients with lung cancer who received at least one dose of ICI between 2015-2020 at The Ohio State University. Pneumonitis cases were documented by the treating oncologist and retrospectively evaluated for agreement between an oncologist and pulmonologist. Patient demographic and clinical characteristics were recorded and summarized between those with and without pneumonitis for the overall cohort, as well as for subsets of patients (stage 4 NSCLC, stage 3 NSCLC, SCLC). Univariate survival analysis with Fine-Gray competing risk model was first used to examine the associations between potential risk factors and ICI pneumonitis. Multivariable analysis was performed between variables identified as significant on univariate analysis. RESULTS: 471 patients with lung cancer were included, of which 402 had Non-Small Cell Lung Cancer (NSCLC) and 69 had Small Cell Lung Cancer (SCLC); 39 developed ICI pneumonitis. Among patients with ICI pneumonitis, a significantly higher proportion had pre-existing interstitial abnormalities compared to those without pneumonitis (57.9% vs 11.3%) (p<0.001). Similar results were seen among subgroups of patients (stage 3 and 4 NSCLC ). Of the variables evaluated, the following were significantly associated with ICI pneumonitis in univariate analysis: pre-existing interstitial abnormalities (hazard ratio of 8.91, 95%CI [4.69, 16.92], p < 0.001), prior chest radiation (hazard ratio 2.81, 95%CI [1.50, 5.28], p=0.001), stage of cancer (hazard ratio of 4.78 for stage 3 cancer, 95%CI [2.42, 9.41] p < 0.001), and type of immunotherapy (hazard ratio of 3.77 for PD1/PDL1, 95%CI [1.75, 8.15], p < 0.001). On multivariable analysis, interstitial abnormalities remained a strong independent risk factor for ICI pneumonitis when controlling for chest radiation and type of immunotherapy (hazard ratio=9.77, 95% CI=(5.17, 18.46), p<0.001). Patients with severe (grade 3-5) pneumonitis had decreased overall survival compared to those with mild (grade 1-2) pneumonitis (p = 0.0013). Pulmonary Function Testing (PFT) abnormalities at both 12 and 18 months prior to ICI initiation were not significantly associated with ICI pneumonitis. CONCLUSIONS: Pre-existing interstitial abnormalities on CT chest and prior chest radiation are strongly associated with development of ICI pneumonitis in patients with lung cancer. This study is the first to evaluate interstitial abnormalities and chest radiation concurrently in patients with lung cancer; we showed that both remain independent risk factors for ICI pneumonitis after accounting for other treatment related risk factors. CLINICAL IMPLICATIONS: Pre-treatment interstitial abnormalities and prior chest radiation could be utilized as part of a risk stratification tool to identify patients at highest risk for developing ICI pneumonitis, a devastating complication associated with higher mortality in more severe cases. This could ultimately impact treatment plans for select individuals identified as high risk. DISCLOSURES: No disclosure on file for Vincent Esguerra No relevant relationships by Kevin Ho No disclosure on file for Kari Kendra No relevant relationships by Mingjia Li No disclosure on file for Gabrielle Lopez No disclosure on file for Gregory Otterson Research funding to institution relationship with BMS Please note: 2018-current Added 03/28/2023 by Dwight Owen, source=Web Response, value=Grant/Research Support Research funding to institution relationship with Merck Please note: 2017-current Added 03/28/2023 by Dwight Owen, source=Web Response, value=Grant/Research Support Research funding to institution relationship with Palobiofarma Please note: 2017-current Added 03/28/2023 by Dwight Owen, source=Web Response, value=Grant/Research Support Research funding to institution relationship with Genentech Please note: 2017-current Added 03/28/2023 by Dwight Owen, source=Web Response, value=Grant/Research Support Research funding to institution relationship with Pfizer Please note: 2017-current Added 03/28/2023 by Dwight Owen, source=Web Response, value=Grant/Research Support No relevant relationships by Carolyn Presley No relevant relationships by Maria Riley No relevant relationships by Matthew Viveiros No relevant relationships by Jing Wang No relevant relationships by Lai Wei No relevant relationships by Alexander Wong No relevant relationships by Songzhu Zhao No relevant relationships by Jessica Zimmer