D1.390 - Hypersensitivity Reactions to Biological Agents in a Tertiary Hospital: A 3.5-Year Retrospective Study

Monoclonal antibodies have revolutionized the treatment of numerous diseases. However, their widespread use has led to an increase in hypersensitivity reactions (HSRs), which may lead to drug discontinuation. This study aims to describe the experience of a tertiary hospital regarding the diagnosis and management of HSRs to biological agents.

A retrospective descriptive study was conducted on patients referred due to HSRs to biological agents from June 2022 to December 2025. Clinical data, serum biomarkers (tryptase and IL-6), and subsequent clinical assessment were analyzed.

Thirty-six patients were included (61% female, mean age 61.6±15.4 years). Biologics were used for hemato-oncology (39%), oncology (31%), and autoimmune diseases (22%). The most frequently implicated agents were rituximab (44%), infliximab (11%) and cetuximab (11%) and other reactions included daratumumab (n=2), pembrolizumab (n=2), avelumab (n=1), brentuximab (n=1), caplacizumab (n=1), obinutuzumab (n=1), and the combinations of pertuzumab/trastuzumab (n=3) and nivolumab/ipilimumab (n=1). Half of the reactions occurred during the first exposure. Most reactions were immediate (94%), 16 probably mast cell-mediated, 11 citokine-mediated and 7 with mixed mechanism.

Four patients underwent skin tests, two with positive results: one was positive on prick for rituximab and the other were positive on intradermal for infliximab.  In patients with immediate HSR, IL-6 was elevated (>7.0 pg/mL) in 10 out of 14 (with normal baseline values), while acute tryptase levels were normal (<11.4 ng/mL) in all 13 patients tested.

Regarding management, 28 patients (78%) were able to maintain the same biological agent, after premedication and infusion rate adjustments (n=12) or desensitization (n=16). Five patients were switched to alternative drugs. Rituximab (n=7) and cetuximab (n=2) were the most frequent drugs in desensitization protocols. Three patients experienced mild reactions during the first desensitization procedure but were able to reach the full dose. Desensitization protocols were successfully simplified in 11 patients.

HSRs to biological agents are heterogeneous, being rituximab, cetuximab, and infliximab the main culprits. The vast majority of patients can safely maintain first-line treatments through therapeutic adjustments or desensitization, depending on the phenotype and severity of the initial reaction.