PD-1 immune checkpoint inhibitors and serious immune-related adverse events

초록

Background: Randomized controlled trials (RCTs) suggested the riskof immune-related adverse events (irAEs) following the use ofprogrammed cell death-1 (PD-1) inhibitors. While the Asian popula-tion is underrepresented in RCTs, the safety of PD-1 inhibitors amongAsians can be different due to the higher prevalence of epidermalgrowth factor receptor mutation and hepatitis B virus infection.Objectives: To estimate the incidence of serious irAEs and their pre-dictors following PD-1 inhibitor use in South Korean patients withnon-small cell lung cancer (NSCLC).Methods: We identified 2,963 patients treated with PD-1 inhibitorsas second-line or above therapy for stage ≥ IIIB NSCLC from a nation-wide healthcare database of South Korea. Patients were followedfrom PD-1 inhibitor initiation with the 1-year exposure risk window.The outcome was defined as simultaneously receiving a pre-defineddiagnosis for potential irAEs and corticosteroids for ≥ 14 days. Cumu-lative incidence of irAEs was estimated using a sub-distribution hazardmodel where death was treated as a competing risk.Results: The 1-year cumulative incidence of serious irAEs was 5.6%(95% confidence intervals: 4.7%-6.6%). Subgroup analysis showedthat PD-1 inhibitor users with the underlying respiratory disease hadan increased risk of irAEs than those without (6.1% vs. 4.0%; Gray'stest P-value, 0.01). PD-1 inhibitor users with the autoimmune diseasehad a slightly higher incidence of irAEs than those without (7.7%vs. 5.4%; Gray's test P-value, 0.19).Conclusions: The incidence of serious irAEs in this Asian lung cancercohort was largely consistent with the findings from RCTs. Patientswith underlying respiratory or autoimmune diseases require vigilantsurveillance and preventive strategies to manage potential irAEs.