- D3.544 - Allergic biomarkers and clinical outcomes in lung cancer patients treated with immune checkpoint inhibitors: a pilot study

Type 2 inflammation biomarkers may influence response and immune-related adverse events (irAEs) to immune checkpoint inhibitors (ICI), but their role in lung cancer remains poorly characterized

Retrospective pilot study including 13 patients with advanced lung cancer receiving ICI-based therapy (pembrolizumab-chemotherapy, n=7; durvalumab-consolidation, n=3; pembrolizumab-monotherapy, n=3). Baseline assessments included total IgE, serum tryptase, aeroallergen skin prick tests, FeNO, peripheral eosinophils, LDH, neutrophil-to-lymphocyte ratio (NLR), Charlson index, PD-L1 expression, and molecular profiling (KRAS, TP53). Clinical outcomes included objective response rate (ORR), progression-free survival (PFS), and irAEs. Spearman correlations assessed biomarker associations.

Median age 65 years (range 50-78); 85% male; ECOG 0-1: 77%; median Charlson: 3. Histology: adenocarcinoma 62%, small-cell 15%, others 23%. KRAS mutations: 50% (6/12 tested); TP53: 46% (6/13); concurrent: 8% (1/13). PD-L1 ≥50%: 33%; 1-49%: 17%; <1%: 50%. LIPI: good 46%, intermediate 38%, poor 15%. Median baseline IgE: 33.8 IU/mL (range 5.49->5000); tryptase: 4.96 µg/L; FeNO: 23 ppb; eosinophils: 190 cells/µL; NLR: 2.94; LDH: 237 U/L. Aeroallergen sensitization: 31% (4/13). One patient had extremely elevated IgE (>5000 IU/mL) with an occupational asthma history. IgE correlated positively with Charlson (ρ=0.62, p=0.024) and negatively with NLR (ρ=-0.57, p=0.044). No associations were observed between allergic biomarkers and KRAS/TP53 status, LIPI, or PD-L1 expression. Clinical outcomes: ORR 83% (10/12 evaluable); 2 complete responses, 8 partial responses. Median PFS: 17.3 months (95%CI not reached due to sample size). Grade ≥2 irAEs occurred in 38% (5/13): pneumonitis (n=1), polyneuropathy (n=1), cytopenias (n=3). No significant associations were identified between baseline allergic biomarkers and tumor response (p>0.05) or irAE incidence, though limited sample size precluded definitive conclusions.

In this exploratory pilot study, elevated IgE was associated with greater comorbidity and, paradoxically, lower systemic inflammation (NLR), suggesting potential interactions between the allergic phenotype and host factors. Despite high ORR and encouraging PFS, no relationship was observed between type 2 biomarkers and treatment outcomes. These preliminary findings warrant validation in larger cohorts to determine whether integrating allergic, genetic, and inflammatory biomarkers can improve predictive models for ICI efficacy and safety.