Incidence of New Malignancies in Severe Asthma: Comparison of Real-World Patients Treated with Benralizumab, Other Biologics, or Non-biologics.

INTRODUCTION: Clinical trials report no increased malignancy risk with benralizumab in severe asthma; however, trial populations are highly selective. To better define real-world safety, malignancy risk was compared among patients treated with benralizumab, other (non-benralizumab) biologics, or non-biologic therapies. METHODS: Data from adults with severe asthma accrued to the International Severe Asthma Registry (ISAR) and a United States severe asthma registry (CHRONICLE) between 1 November 2017, and 31 December 2023, were analyzed. Cohorts were defined by exposure to benralizumab, other asthma biologics, and non-exposure to biologic therapies. First new-onset malignancies were assessed. Incidence per 1000 person-years (PY) and adjusted incidence rate ratios (aIRR) were estimated with an inverse probability-weighted Poisson model, with propensity scores incorporating demographics, comorbidities, baseline asthma medication, systemic steroid use, and relevant medical history, with residual adjustment for age, sex, body mass index, region, and smoking. RESULTS: Among 12,493 patients, 43,434.8 PY were accrued (benralizumab, 7749.1 PY; other biologics, 21,054.1 PY; non-biologics, 14,631.6 PY), with a median (range) follow-up of 3.3 (0-6.2) years across cohorts. Seventy-five patients reported new malignancies: benralizumab, 17 (0.7%); other biologics, 34 (0.6%); and non-biologics, 24 (0.5%). Weighted, fully adjusted incidence rates were 1.3 versus 1.1 per 1000 PY for benralizumab versus other biologics (aIRR 1.2, 95% CI 0.79-1.81) and 1.8 versus 1.7 per 1000 PY for benralizumab versus non-biologics (aIRR 1.1, 95% CI 0.70-1.59). CONCLUSIONS: This large observational study with up to 6 years of follow-up found no increased malignancy risk with benralizumab versus other therapies in patients with severe asthma.