P1.16-06 Early Changes in Pulmonary Function Are Associated with Development of Pneumonitis in NSCLC Patients Receiving Immune Checkpoint Blockade

Abstract

Checkpoint inhibitor pneumonitis (CIP) is an immune-related adverse event of immune checkpoint inhibitors (ICI). Pulmonary function test (PFT) changes have been noted in patients receiving drugs such as bleomycin, and PFTs are routinely used to monitor for lung toxicity in such patients. We retrospectively analyzed PFTs in ICI-treated non-small cell lung cancer (NSCLC) patients to identify PFT changes associated with ICI use, and determine whether CIP modified this association. The study cohort included NSCLC patients who were treated with PD-(L)1 ICI as standard-of-care or part of a clinical trial at Johns Hopkins from 1/2007 - 7/2017 and had ≥1 PFT in the year preceding and/or following ICI initiation. The primary outcomes of interest were forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio. Linear regression based on generalized estimating equations (GEE) was used to evaluate changes overall and by CIP status (CIP+: Patients who develop CIP, CIP-: Patients who do not develop CIP). A total of 58 patients (43 CIP-, 15 CIP+) were included. Median age was 66y and 96% of patients were current/former smokers. 52% had adenocarcinoma and 45% had squamous histology. 75% had stage III/IV disease at initial diagnosis. Patients received single agent PD-(L)1 ICI (77%), ipilimumab+nivolumab (ipi/nivo) (12%), and novel PD-(L)1 ICI (10%). Compared to CIP- patients, CIP+ patients were more likely to have squamous histology (67% vs. 34%) and receive ipi/nivo (27% vs 7%). In the overall study cohort, ICI initiation was associated with a 0.335L reduction in FEV1 (95% CI: -0.713, 0.042), 0.747L reduction in FVC (-1.21, -0.28), and 0.061 increase in FEV1/FVC (0.006, 0.116) consistent with restrictive lung physiology. Compared to CIP- patients, CIP+ patients had a 0.35L (-0.724, 0.013) lower FEV1 and 0.516L (-1.06, 0.02) lower FVC, while FEV1/FVC did not differ (-0.07, 0.07). The rate of change of FEV1/FVC over time was significantly higher among patients with vs without CIP (p<0.05). Our data suggest that initiation of PD-(L)1 ICI is associated with progressively restrictive lung function changes on PFTs (increased FEV1/FVC) irrespective of CIP development. Furthermore, our results indicate that patients who eventually develop CIP may have an altered respiratory physiology prior to ICI initiation, with longitudinal changes in lung function that differ when compared to CIP- patients who receive checkpoint blockade. To further characterize PFT changes associated with CIP, a prospective study assessing serial PFTs in NSCLC patients receiving ICIs is underway.