Health care resource utilization and cardiovascular outcomes in lung cancer patients receiving immunotherapy in relation to smoking status: A retrospective cohort study and systematic review

The relationship between smoking status and clinical outcomes in lung cancer patients treated with immune checkpoint inhibitors (ICIs) has not been well established. We aimed to evaluate healthcare resource utilization (HCRU) and cardiovascular outcomes among lung cancer patients receiving ICIs, grouped by their smoking history. This retrospective cohort study included patients with non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) treated with ICIs at Mercy Hospital Fort Smith between January 1, 2020, and December 31, 2022. Follow-up extended through December 2023. Smoking status was categorized as current, former, or never smoker. The primary endpoint was HCRU, including emergency room (ER) visits and hospital admissions during immunotherapy. Secondary endpoints included the incidence of cardiovascular events, immune-related adverse events (irAEs), and early treatment discontinuation. A systematic review of relevant studies published from 2015 to early 2024 was also conducted. Of 122 patients included (median age 72 years), 43% were current smokers, 48% former smokers, and 9% never smokers. ER utilization occurred in 85% of patients. Cumulative pack-years were significantly associated with ER visits (OR 1.03 per pack-year; 95% CI 1.00–1.06; p=0.04; AUC=0.59). Cardiovascular events occurred in 20% of patients, the highest among durvalumab recipients (38%). irAEs occurred in 25% of patients, with former/never smokers more likely to experience irAEs than current smokers (77% vs. 23%; p<0.01). Current smokers had higher rates of early treatment discontinuation (60% vs. 49%; p=0.02). Multivariate adjustment confirmed our observed associations. Smoking status significantly correlates with healthcare utilization and immune-related adverse events in lung cancer patients receiving ICIs. These findings highlight the need for tailored clinical strategies based on smoking history.