Dupilumab and lymphoma risk among patients with asthma: a population-based cohort study

Background Dupilumab is approved for the treatment of atopic dermatitis, asthma, and other allergic diseases. Recent studies suggest that patients with atopic dermatitis receiving dupilumab are at a higher risk of developing cutaneous lymphoma. This study aimed to investigate the risk of lymphoma among patients with asthma receiving dupilumab. Methods This population-based cohort study included patients in the United States with asthma who initiated dupilumab or the active comparator (combination therapy with inhaled corticosteroids (ICS) plus long-acting β-agonists (LABA), or ICS/LABA), between 2018 and 2024. Propensity score matching was used to balance baseline characteristics between groups. The primary outcome was new-onset lymphoma, and secondary outcomes included other malignancies and all-cause mortality. Results A total of 14 936 dupilumab-treated and 734 126 ICS/LABA-treated patients with asthma were included. After propensity score matching, dupilumab-treated patients were found to have a higher risk of lymphoma (54 versus 43 cases, hazard ratio (HR) 1.79, 95% CI 1.19–2.71), especially T-cell and natural killer (NK)-cell lymphomas (19 versus ≤10 cases, HR 4.58, 95% CI 1.82–11.53). There was no significant difference in incidence of other malignant neoplasms. Dupilumab was also associated with significantly lower all-cause mortality (328 versus 793 deaths, HR 0.65, 95% CI 0.57–0.74). Conclusions Dupilumab treatment was associated with lower all-cause mortality among patients with asthma, despite increased risk of lymphoma, particularly T-cell and NK-cell lymphomas. These findings highlight the need for long-term surveillance and further research into the immunological mechanisms underlying dupilumab-associated lymphoma in asthma.