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.

[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.