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

BACKGROUND Dupilumab is approved for treatment of atopic dermatitis, asthma and other allergic diseases, including atopic dermatitis. Recent studies suggest that patients with atopic dermatitis receiving dupilumab are at higher risk of developing cutaneous lymphoma. This study aimed to investigate the risk of lymphoma among asthma patients treated with dupilumab. METHODS This population-based cohort study included U.S. patients with asthma who initiated dupilumab or the active comparator (combination therapy with inhaled corticosteroids [ICS] plus long-acting beta 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 the secondary outcomes were other malignancies and all-cause mortality. RESULTS A total of 14 936 dupilumab-treated and 734 126 ICS/LABA-treated asthma patients were included. After propensity score matching, dupilumab-treated patients were found to have a higher risk of lymphoma (n=54 versus 43 cases, hazard ratio [HR]=1.79, 95% CI 1.19, 2.71), especially T and natural killer (NK) cell lymphomas (n=19 versus <10, HR=4.580, 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 (n=328 versus 793, HR=0.65, 95% CI 0.57, 0.74). CONCLUSIONS Dupilumab treatment was associated with lower all-cause mortality among asthma patients despite increased risk of lymphoma, particularly T 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.