Incidence, outcomes, and risk factors of acute immune checkpoint inhibitor (ICI) pneumonitis post-chemoradiation with durvalumab for patients with locally advanced non-small cell lung cancer (LA-NSCLC): A population-based multicenter study.
Authors: Lim Chloe , Ghosh Sunita , Morrison Hali , Meyers Daniel E. , Stukalin Igor , Dolter Samantha , Grosjean Heidi A.I. , Kerba Marc , Hao Desiree , Pabani Aliyah 
Published: June 2023

8561

Background: The PACIFIC trial has drastically changed the LA-NSCLC treatment paradigm and improved survival outcomes with consolidation durvalumab post-chemoradiotherapy. Despite these promising results, real-world practice has demonstrated that ICI pneumonitis can have significant clinical complications and terminate consolidation therapy prematurely. This study aimed to identify clinical predictors, outcomes, and healthcare utilization in ICI pneumonitis in LA-NSCLC patients who received consolidation durvalumab in real-world practice. Methods: Using the Alberta Immunotherapy Database, we retrospectively evaluated all NSCLC patients who received durvalumab in Alberta, Canada from January 2018 to December 2021. Pneumonitis cases were identified based on radiographic changes and oncologists’ clinical assessments. We examined incidence and predictive values of severe pneumonitis (≥grade 3), with secondary outcomes of overall survival (OS) and time-to-treatment failure (TTF). Exploratory multivariate analyses were performed to identify predictive values to developing severe pneumonitis and worse OS/TTF. Results: Of 189 total patients, most were ECOG 0-1 (91%) and had partial response from chemoradiation (85%) prior to durvalumab. 49% received full year of therapy (n = 93). Median TTF was 11.2 months, and median OS of 19.7 months with 1-year OS 64% (n = 121). 26% (n = 49) developed any grade of pneumonitis. 9% (n = 17) had severe pneumonitis. Corticosteroids were administered to 86% of the pneumonitis patients (n = 42); 53% (n = 26) required admission. 13% (n = 9) of deaths were attributed to pneumonitis. Male gender and pre-existing autoimmune condition were associated with severe pneumonitis whereas V20 (percentage of irradiated lung volume ≥20Gy) was associated with developing any grade pneumonitis. In multivariable analysis, male gender and V20 was significantly associated with worse OS whereas older age, smoking status, pneumonitis, and male gender with lower TTF. Pneumonitis development was found to be an independent risk factor for worse OS (p = 0.038) and TTF (p = 0.007). Conclusions: We report a pneumonitis incidence comparable to prior retrospective studies and higher rate of severe pneumonitis compared to PACIFIC trial. Our results corroborate that V20, a previously established risk factor for durvalumab associated pneumonitis, is a significant predictor for developing pneumonitis and worse OS. In contrast to smaller retrospective studies, we observed male gender and pre-existing autoimmune conditions appear to predict severe durvalumab associated ICI pneumonitis. These results affirm the importance of careful patient selection for safe completion of consolidation durvalumab in real-world LA-NSCLC population.