Rapid drug desensitization in seven patients with delayed hypersensitivity reactions to biologics and targeted therapies: Reason, successes, and failures.

Backround: Rapid drug desensitization (RDD) is commonly used for immediate drug hypersensitivity reactions (DHR) across various drugs. In delayed DHRs, the conventional approach is slow desensitization; however, limitations may arise due to drug-specific or disease-related factors. With the increasing role of targeted molecular drugs in delayed DHRs, data on the efficacy of RDD in these contexts remain scarce. Objective: This case series aims to explore the rationale and outcomes of RDD in managing delayed DHRs associated with targeted therapies. Methods: We analyzed data from patients referred to a tertiary university hospital's drug allergy outpatient clinic between January 2021 and April 2024. The subjects experienced delayed DHRs during treatment with targeted drugs and, subsequently, underwent RDD. Results: The drugs administered via RDD included bevacizumab, rituximab, daratumumab, lenalidomide, bortezomib, and carfilzomib. The index reactions included maculopapular eruptions (MPE), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). Delayed breakthrough reactions were observed in four of seven patients. RDD with bortezomib was unsuccessful in all three patients, and delayed reactions were observed in all patients with severe cutaneous adverse reactions (AGEP and DRESS). Conclusion: Suggesting significant success of RDD for delayed DHRs induced by targeted therapies may be overly optimistic. Nevertheless, four of seven patients, including one with AGEP, were able to continue their treatment. Managing patients with advanced diseases and delayed DHR poses notable challenges. The risk to patient survival from withholding life-saving medication must be weighed against the risks of desensitization. The low sensitivity of skin tests and the critical waiting period complicate decision-making. Given the unique contribution of targeted agents in the treatment of severe, life-threatening diseases, further research on desensitization is warranted.