Risk of Lymphoma in Patients with Asthma Treated with Dupilumab Compared with Other Biologic Agents: A Retrospective Cohort Study.

Abstract

Dupilumab, an interleukin-4 receptor α antagonist, has transformed the treatment of severe asthma but has been linked to reports of lymphoma, particularly cutaneous T-cell lymphoma. Whether lymphoma risk differs between dupilumab and other asthma biologics remains unclear. What is the comparative incidence of lymphoma among adult asthma patients treated with dupilumab versus omalizumab, mepolizumab, or benralizumab? We conducted a retrospective cohort study using the TriNetX global federated health research network. Adults with asthma initiating dupilumab, omalizumab, mepolizumab, or benralizumab between 2015 and 2025 were identified. Propensity score matching balanced baseline demographic and clinical characteristics. The primary outcome was lymphoma incidence. Secondary outcomes included lung, breast, and prostate cancers. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. After matching, 10,841 dupilumab users were compared with 10,841 omalizumab users, 8,088 mepolizumab users, and 7,330 benralizumab users. Over up to 5 years of follow-up, lymphoma incidence rates per 1,000 person-years were 1.5 versus 0.8 (HR, 1.25; 95% CI, 0.78-2.00) for dupilumab versus omalizumab, 1.5 versus 1.5 (HR, 0.91; 95% CI, 0.53-1.56) versus mepolizumab, and 1.5 versus 1.7 (HR, 0.84; 95% CI, 0.47-1.51) versus benralizumab. No significant differences were observed for breast, lung, or prostate cancer. No statistically significant differences in lymphoma incidence were observed between dupilumab and other biologics. These findings provide comparative reassurance regarding lymphoma risk with dupilumab over up to 5 years of follow-up.