(534) Gastrointestinal Bleeding in Checkpoint Inhibitor Therapy for Metastatic Lung Cancer

Introduction: Several immune checkpoint inhibitor (ICI) therapies have been FDA-approved for lung cancer since 2015. These include programmed death receptor 1 (PD-1) and ligand 1 (PD-L1)-targeting agents. ICIs have been associated with numerous immune related adverse events (irAEs), which can affect any organ system. Thromboembolic disease and bleeding are poorly understood irAEs.

Methods: We queried the TriNetX Research Network (aggregating the deidentified health record data of >131 million patients across 5 countries) for patients with lung cancer (ICD-10-CM C34) and metastasis (TNM stage M1) between 03/2015 – 08/2023. We defined a cohort who received 1 of 4 ICIs (pembrolizumab, ipilimumab, atezolizumab, or nivolumab) within 1 year of diagnosis and a non-recipient cohort. We compared 1-year incidence of gastrointestinal bleeding [GIB, defined as hematemesis (K92.0) or melena (K92.1)] from diagnosis (and ICI receipt, where relevant). We created propensity score matched (PSM) sub-cohorts balancing 18 demographic and comorbidity variables and repeated the comparison. Finally, we compared outcome incidences between PD-1 and PD-L1 ICI recipients with lung cancer prior to and following matching.

Results: Of 111,827,983 patients (aged 18 – 90) there were 428,096 with lung cancer (0.4%). 16,963 (4.0%) carried the M1 designation and the majority (>90%) were located within the U.S. We compared a cohort of 2,642 ICI recipients (15.6%) to 11,900 ICI non-recipients (70.2%). 1-year incidence of GIB among ICI recipients was 6.1 vs 4.5% (OR 1.4, CI 1.2 – 1.7, p< 0.01), while a repeat analysis among PSM-generated like sub-cohorts found an incidence of 11.4 vs 8.3% (OR 1.4, CI 1.2 – 1.7, p< 0.01). PD-1 recipients had a slightly higher risk of GIB than PD-L1 recipients prior to (7.1 vs 6.5%, OR 1.1, p=0.04) and following matching (7.3 vs 6.4, OR 1.1, p=0.04). The standardized difference was < 0.1 in matched covariates.

Conclusions: Our analysis showed excess gastrointestinal bleeding in ICI recipients with metastatic lung cancer compared to non-recipients. In a separate analysis, there was a higher risk of GIB among PD-1 versus PD-L1 recipients with lung cancer. Clinicians caring for lung cancer patients receiving ICIs should be cognizant of the increased incidence of bleeding disorders to which this therapy is associated.