From chemotherapy allergy to tolerance: Desensitization as a safe alternative in oncology.

Abstract

11057 Background: Hypersensitivity reactions (HSRs) are a significant challenge in oncology, often leading to treatment modifications or interruptions. Rapid Drug Desensitization (RDD) is a method to reintroduce chemotherapeutic agents and monoclonal antibodies in patients with previous HSRs. This study focuses on safety, comparing the severity of initial HSRs with breakthrough reactions (BTRs) during desensitization. Methods: An observational, ambispective study was conducted from August 2020 to August 2024 at the University Hospital in Mexico. Patients with HSRs underwent RDD using a 12-step, 3-bag protocol. HSR severity was classified using Brown’s scale. The primary endpoint was BTR severity compared to initial reactions, with secondary endpoints assessing BTR frequency and RDD completion rates. Data were sourced from electronic medical records under a protocol reviewed and approved by the hospital's research ethics committee. Inclusion required documentation of HSRs, the need to continue treatment with the implicated drug, and completion of the RDD protocol. Missing severity data were inferred from clinical notes or excluded. Chi-square tests compared severity grades (mild, moderate, severe) between initial reactions and BTRs, including cases without reactions for comprehensive analysis. Proportional frequencies were applied to address the difference in sample size. Results: A total of 927 RDD procedures were performed in 219 patients, with 84% female and a median age of 43 years. The severity of initial reactions was classified as mild in 12.1%, moderate in 43.3%, and severe in 44.6%. During the 927 desensitizations, breakthrough reactions occurred in only 8.6% of cases, distributed as mild (4.5%), moderate (1.8%), and severe (2.3%). Chi-square analysis confirmed a statistically significant difference in severity distribution between initial HSRs and BTRs (χ² = 834.72, p < 0.0001). This demonstrated a substantial reduction in severity for BTRs compared to initial reactions. Despite the occurrence of BTRs, all patients completed the RDD protocol, received the full therapeutic dose, and no fatalities were reported. Conclusions: The comparison between initial HSRs and breakthrough reactions during RDD highlights the distinct nature of these events: initial HSRs represent baseline sensitivity, whereas BTRs occur as controlled outcomes during desensitization. The analysis confirms that desensitization is a safe and effective tool in oncology, significantly reducing both the frequency and severity of breakthrough reactions compared to initial reactions, ensuring treatment continuity and minimizing risks for patients. Severity distribution of initial HSRs and BTRs. Severity Mild (%) Moderate (%) Severe (%) Total (%) Reference Population Initial HSRs 27 (12.3) 95 (43.3) 97 (44.2) 219 (100) 219 patients BTRs 42 (4.5) 17 (1.8) 21 (2.3) 80 (8.6) 927 desensitizations