Immune checkpoint inhibitors and myocarditis in advanced non-small cell lung cancer: a nationwide cohort study.

Objective: Evidence suggests immune checkpoint inhibitor (ICI) can increase the risk of myocarditis. We investigated it in a large national cohort in China.

Methods: Patients with stage IIIB-IV non-small cell lung cancer (NSCLC) using data from China's National Anti-Tumor Drug Surveillance System between January 2013 and December 2021. Exposure density sampling was applied to control for immortal time bias. Multivariate Cox regression with time-dependent exposures was used to examine the association between ICI therapy and the incidence of myocarditis while controlling for confounders.

Results: 55,219 patients were included. The median age was 61 years, and 62% were males. At one-year follow-up (median 335 days), there were 26 cases of myocarditis among ICI users and 28 cases among ICI non-users (a cumulative incidence of 4.8 and 0.6 per 1000 person-years respectively). The adjusted hazard ratio (HR) of myocarditis for ICI users was 7.41 (95% confidence interval [CI]: 3.29-16.67). For programmed cell death protein 1 inhibitor users the HR was 8.39 (95% CI: 3.56-19.77). No significant interactions were observed in subgroup analysis. The results remained unchanged in sensitivity analyses.

Conclusions: This study showed that ICI therapy considerably increased the risk of myocarditis, supporting the need for closer monitoring of patients receiving ICI therapies.