Association of early dynamic changes in peripheral blood immune-inflammatory indices with subsequent acquired resistance to immune checkpoint inhibitors in advanced non-small cell lung cancer: a landmark analysis.

BACKGROUND

Acquired resistance to immune checkpoint inhibitors (ICIs) remains a major challenge in advanced non-small cell lung cancer (NSCLC). This study evaluated whether early dynamic changes in peripheral inflammatory and nutritional indices predict subsequent acquired resistance.

METHODS

This retrospective landmark cohort included 138 patients with advanced NSCLC who achieved disease control after ICI-containing therapy. Systemic immune-inflammation index (SII), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio, prognostic nutritional index (PNI), and lactate dehydrogenase were assessed at baseline and after two ICI cycles. Landmark and time-dependent Cox regression analyses evaluated associations with subsequent progression-free survival (PFS).

RESULTS

During follow-up, 68 patients developed acquired resistance. After adjustment, increased ΔSII (HR = 2.05, 95% CI 1.32-3.18, p = 0.001), decreased ΔPNI (HR = 1.76, 95% CI 1.14-2.71, p = 0.010), and increased ΔdNLR (HR = 1.69, 95% CI 1.10-2.60, p = 0.016) were independently associated with shorter PFS. Time-dependent analyses further confirmed associations of longitudinal SII, PNI, and dNLR trajectories with disease progression.

CONCLUSIONS

Early dynamic changes in SII, PNI, and dNLR are associated with subsequent acquired resistance after initial disease control in advanced NSCLC receiving ICI-containing therapy and may support early risk stratification.