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.

Abstract

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.