D1.367 - Risk factors for immediate hypersensitivity reactions to rituximab

Rituximab is widely used for the treatment of hematologic malignancies and autoimmune diseases; however, immediate hypersensitivity reactions may limit its use and pose significant clinical challenges. While infusion-related reactions are well recognized, data on risk factors for immediate hypersensitivity reactions in adult patients remain limited, particularly in the context of biosimilar use and product switching.

We conducted a retrospective case–control study of adult patients who received rituximab at a tertiary care center between January 2014 and August 2025. Patients who developed immediate hypersensitivity reactions within 1–6 hours of rituximab administration were compared with systematically sampled controls without hypersensitivity reactions, using a 1:4 case–control ratio. Baseline demographic, clinical, laboratory, and treatment-related variables were analyzed. Univariate and multivariable logistic regression analyses were performed to identify factors associated with immediate hypersensitivity reactions.

A total of 2,025 patients received rituximab during the study period. Among these, 130 patients were included in the analysis, comprising 26 patients with immediate hypersensitivity reactions and 104 controls. Baseline demographic characteristics, comorbidities, laboratory parameters, rituximab dosing, infusion rates, and corticosteroid premedication were largely comparable between groups. Patients with hypersensitivity reactions had a higher prevalence of allergic rhinitis (19.2% vs. 2.9%). Immediate hypersensitivity reactions occurred predominantly during the first three rituximab administrations and demonstrated heterogeneous clinical endotypes, including Type I, cytokine release, and mixed-type reactions. In multivariable analysis, switching from originator to biosimilar rituximab (odds ratio [OR] 8.02; 95% confidence interval [CI] 1.22–52.63) and underlying allergic rhinitis (OR 8.80; 95% CI 1.90–40.63) were independently associated with immediate hypersensitivity reactions.

Switching from originator to biosimilar rituximab and the presence of allergic rhinitis were independently associated with immediate hypersensitivity reactions in adult patients. These findings highlight the importance of immunologic predisposition and treatment-related factors in rituximab hypersensitivity and support closer monitoring of high-risk patients, particularly during early treatment cycles.