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Background <p>Although allergic predisposition may modulate antitumor immunity, its influence on immune checkpoint blockade remains unclear. We investigated whether a documented drug allergy history affects the outcomes of PD-(L)1 inhibitors in advanced non-small cell lung cancer (NSCLC).</p> Methods <p>We retrospectively analyzed 246 patients with stage III–IV NSCLC treated with PD-(L)1 inhibitors at West China Hospital from October 2019 to October 2024, with follow-up through May 2025. Patients were grouped according to drug allergy history. Baseline imbalances were corrected using 1:2 propensity score matching (caliper 0.2) and inverse probability of treatment weighting. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and immune-related adverse events (irAEs).</p> Results <p>Before adjustment, allergy-positive patients (n = 49) showed higher 1-year PFS than controls (54.4% vs. 35.7%, p = 0.019). After matching, median PFS remained longer (13.6 vs. 6.6&#xa0;months; hazard ratio 0.61, 95% CI 0.40–0.91, p = 0.017), and 1-year PFS improved (57.0% vs. 33.4%, p = 0.009), whereas 3-year PFS, OS, and ORR were comparable. Weighted analyses and multiple sensitivity tests corroborated these findings. Overall incidences of Grade ≥ 2 or ≥ 3 irAEs were similar; although Grade ≥ 2 gastrointestinal irAEs trended higher in the allergy cohort (6.1% vs. 1.0%, p = 0.054).</p> Conclusions <p>A history of drug allergy predicts early clinical benefits, particularly superior 1-year PFS, from PD-(L)1 blockade in advanced NSCLC without increasing severe irAEs. Prospective multicenter studies are needed to confirm these findings and elucidate the underlying mechanisms.</p>

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Drug allergy history predicts early progression-free survival benefit from PD-(L)1 inhibitors in advanced non-small cell lung cancer: a retrospective cohort study

  • 期刊论文

  • 发表日期：

    2025年10月21日

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  • Wenhao Zhao,
  • Min Yu,
  • Youling Gong,
  • Meijuan Huang,
  • Jianxin Xue,
  • You Lu

摘要

Background

Although allergic predisposition may modulate antitumor immunity, its influence on immune checkpoint blockade remains unclear. We investigated whether a documented drug allergy history affects the outcomes of PD-(L)1 inhibitors in advanced non-small cell lung cancer (NSCLC).

Methods

We retrospectively analyzed 246 patients with stage III–IV NSCLC treated with PD-(L)1 inhibitors at West China Hospital from October 2019 to October 2024, with follow-up through May 2025. Patients were grouped according to drug allergy history. Baseline imbalances were corrected using 1:2 propensity score matching (caliper 0.2) and inverse probability of treatment weighting. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and immune-related adverse events (irAEs).

Results

Before adjustment, allergy-positive patients (n = 49) showed higher 1-year PFS than controls (54.4% vs. 35.7%, p = 0.019). After matching, median PFS remained longer (13.6 vs. 6.6 months; hazard ratio 0.61, 95% CI 0.40–0.91, p = 0.017), and 1-year PFS improved (57.0% vs. 33.4%, p = 0.009), whereas 3-year PFS, OS, and ORR were comparable. Weighted analyses and multiple sensitivity tests corroborated these findings. Overall incidences of Grade ≥ 2 or ≥ 3 irAEs were similar; although Grade ≥ 2 gastrointestinal irAEs trended higher in the allergy cohort (6.1% vs. 1.0%, p = 0.054).

Conclusions

A history of drug allergy predicts early clinical benefits, particularly superior 1-year PFS, from PD-(L)1 blockade in advanced NSCLC without increasing severe irAEs. Prospective multicenter studies are needed to confirm these findings and elucidate the underlying mechanisms.