Breakthrough reactions during rapid drug desensitization: Clinical outcome and risk factors

Background: Severe hypersensitivity reactions (HSRs) interfere with the administration of necessary drugs for patients; drug desensitization can be a good alternative strategy. Although rapid drug desensitization (RDD) has been shown to be safe and effective, some patients still experience breakthrough reactions (BTRs) during desensitization. Objective: We aimed to estimate clinical outcomes of RDD and to identify risk factors for BTR. Methods: From January 2015 to December 2017, retrospective analysis was done in cancer patients with HSRs to chemotherapy and monoclonal antibody who underwent 3-bag, 12-step RDD in Asan Medical Center. Results: A total of 58 patients (42 females; mean age, 54.7 ± 11.0) underwent 234 desensitization procedures. The most common underlying malignancy was gynecologic cancer (n = 26, 44.8%), and platinum-based drugs were common target drugs (135 cases of 36 patients). Twenty-six of 58 patients (44.8%) experienced 56 BTRs, whereas 178 cases (76.1%) of total desensitization did not show any reactions. Among them, 12 patients (20.7%) had moderate BTRs requiring systemic steroids, and 3 (5.1%) experienced severe BTRs requiring epinephrine administration. Logistic regression analysis revealed more severe initial HSRs (OR = 17.94, 95% CI = 1.78-181.68, P = .015), drug allergy history (OR = 7.83, 95% CI = 1.48-41.44, P = .035), and frequency of exposure to the chemotherapeutic agents (OR = 1.14, 95% CI = 1.01-1.28, P = .016) increased the risk of moderate to severe BTR. Conclusion: The standardized 12-step protocol for RDD was effective and safe for most patients. Severity of initial HSR, history of drug allergy, and previous high exposure to the chemotherapeutic agent showed a positive correlation with BTR above moderate grade. Studies are needed to propose an individualized protocol according to patient-specific risk assessment.