Impact of irae characteristics on efficacy of consolidative immunotherapy following chemoradiotherapy in locally advanced NSCLC.

BACKGROUND: Consolidative PD-L1 inhibitors after concurrent chemoradiotherapy (cCRT) have become standard care in locally advanced non-small cell lung cancer (LA-NSCLC). However, the correlation between immune-related adverse event (irAE) characteristics and patient outcomes remains unclear. METHODS: This retrospective study enrolled LA-NSCLC patients who received consolidative PD-L1 inhibitors after CRT at four cancer centers. Patients who received CRT alone were also included for comparison. Associations between irAE characteristics, frequency, timing, affected systems, and severity, and progression-free survival (PFS) and overall survival (OS) were assessed. Tumor immune microenvironment (TIME) features were analyzed to identify subpopulations at higher risk of severe irAEs. RESULTS: Among 107 patients, 59 (55.1%) developed irAEs; 89.8% were grade 1-2 and 10.2% grade 3-4. Patients with irAEs had significantly longer PFS than those without. Late-onset, single-system, endocrine, and mild irAEs predicted better PFS. In contrast, patients with severe irAEs had worse survival than those without ICI consolidation. TIME analysis revealed that severe irAEs were associated with higher CD103(+)CD8(+) T cells infiltration. A > 1.545% cutoff for CD103(+)CD8(+) T cells may help identify patients less likely to benefit from PD-L1 inhibitor consolidation. CONCLUSIONS: Occurrence of irAEs, particularly late-onset, single-system, or grade 1-2 correlated with greater benefit from consolidative PD-L1 inhibitors in LA-NSCLC. Conversely, severe irAEs predict poorer survival, even compared to no ICI consolidation. Elevated CD103(+)CD8(+) T cell infiltration may serve as a biomarker to identify patients at risk of severe irAEs who may not benefit from immunoconsolidation therapy.