The price of a breath: The economic and mortality burden of checkpoint inhibitor pneumonitis (2016–2020).

Abstract

12142 Background: The landscape of oncologic toxicity has drastically changed because of the rapid introduction of Immune Checkpoint Inhibitor (ICI) indications, ranging from the treatment of melanoma to thoracic cancers. Immune-related adverse events (irAEs) are a novel range of toxicities brought about by the rapid growth of ICI. The overall national burden of severe inpatient toxicities is still unknown, despite the well-described outpatient care of irAEs. We measured the prevalence, mortality, and financial impact of severe irAEs necessitating hospitalization using the Nationwide Inpatient Sample (NIS). Methods: We evaluated adult hospitalizations secondary to major irAEs (pneumonitis, colitis, hepatitis, and endocrinopathies) using ICD-10-CM codes for a retrospective cohort analysis of the National Inpatient Sample database from 2016 to 2020. Only patient with cancer diagnosis associated complications were included to reduce confounders. Statistical evaluations and outcomes were generated using STATA version 19. The use of mechanical ventilation, total hospital charges, and in-hospital mortality were the major outcomes. Temporal trends and mortality factors were examined using survey-weighted regression models. Results: We identified a weighted national cohort of 109,225 irAE-related hospitalizations from 2016 to 2020. Epidemiology: Immune-mediated Colitis was the dominant driver of volume (54.6%) for inpatient admission, followed by Pneumonitis (22.2%) and Hepatitis (18.2%). The proportion of admissions attributable to Pneumonitis was increased from 21.1% in 2016 to 24.0% in 2020 (p < 0.001), coincident with expanded ICI use in lung cancer. Outcomes & Acuity: Pneumonitis was associated with the longest mean length of stay (LOS) of 6.9 days and the highest raw mortality (7.8%) compared to Colitis (1.6%). In multivariable analysis, Pneumonitis was the strongest independent predictor of in-hospital mortality (aOR 4.98; 95% CI 4.12–6.02; p < 0.001)relative to Colitis. Conversely, female sex was associated with a significant survival advantage (aOR 0.76; p = 0.001). Economic Burden: Pneumonitis was the most resource-intensive toxicity (Mean Charge: $74,298 vs. $43,831 for Colitis). The aggregate national hospital bill for irAEs rose from $1.14 Billion in 2016 to a peak of $1.75 Billion in 2020. Conclusions: Pneumonitis is the primary cause of death and economic expense, whereas colitis is the primary cause of irAE hospitalizations. Between 2016 and 2020, the total cost of hospitalization in the United States almost doubled, reaching approximately $1.75 billion per year. Health systems need to prepare for an increase in high-acuity, resource-intensive pulmonary toxicity as ICI indications spread into the adjuvant environment.