Management of Rituximab-Associated Hypersensitivity Reactions with Successfully Applied Desensitization Protocols: A Clinical Experience of 46 Infusions in 11 Patients

Background: Rituximab, a chimeric monoclonal anti-CD20 antibody, is widely used in various malignant and benign conditions, including leukemia, lymphoma, rheumatoid arthritis, and systemic lupus erythematosus. However, some patients may develop early or delayed hypersensitivity reactions (HSRs) following rituximab infusion, which can limit therapy continuation. Objective: This study aimed to evaluate patients who developed HSRs during rituximab treatment and report the outcomes of desensitization protocols implemented to allow treatment continuation. Methods: We retrospectively analyzed 11 patients who experienced allergic reactions or anaphylaxis during rituximab therapy at the Adult Hematology Department between 2022 and 2024. Demographic data, underlying diseases, timing and type of HSRs, and details of the desensitization protocols were recorded. Results: Among the 11 patients, 8 were male and 3 were female, with a median age of 56 years (range: 19–72). Eight patients had CD20-positive non-Hodgkin lymphoma (NHL) and three had acute B-lymphoblastic leukemia (B-ALL). HSRs occurred during the first rituximab exposure in 9 patients, at the fourth dose in 1 patient, and at the eighth dose in another. Symptoms included widespread rash, pruritus, flushing, chills, shivering, dyspnea, dysphagia, back pain, dizziness, syncope, and throat discomfort. All patients were consulted by the Allergy and Immunology Clinic. Based on prick and intradermal test (IDT) results and the planned rituximab dose, desensitization protocols consisting of a 3-dilution/12-step and a 4-dilution/16-step regimen were prepared. Premedication with 40 mg methylprednisolone and 1 ampoule of pheniramine maleate was administered prior to all procedures. In one patient, despite the 12-step protocol, HSR (chest pain and dyspnea) occurred, and the 16-step/4-dilution protocol was successfully applied. Overall, 46 desensitization procedures were successfully completed in 11 patients. Conclusion: Although the number of patients was limited, our findings indicate that in patients with hematologic malignancies receiving rituximab who develop early HSRs, desensitization represents a safe and effective strategy before considering treatment modification. These results support that, in appropriately selected patients, desensitization protocols are an important approach to continue therapy without interruption while minimizing adverse reactions.