Clinical outcomes and risk factors associated with breakthrough reactions in chemotherapy desensitization

Background: Rapid drug desensitization (RDD) is a safe and effective option for patients who are hypersensitive when no alternatives are available; however, breakthrough reactions (BTR) may still occur. Objective: This study aimed to evaluate chemotherapeutic RDD outcomes and identify risk factors for BTRs. Methods: This retrospective study included patients who underwent chemotherapeutic RDD between 2019 and 2023 at a tertiary adult allergy clinic. BTR rates and potential risk factors were assessed. Results: Among 197 patients with chemotherapy-induced immediate hypersensitivity reactions, 132 (95 women [72.0%]) were included in the final analysis. A total of 552 RDD procedures (range, 1-17) were performed, most frequently with carboplatin (43.1%), oxaliplatin (28.0%), and cisplatin (10.6%). Among these patients, 45 (34.0%) experienced a total of 72 BTRs (13.0%). BTRs occurred at a median of 2 cycles (range, 1-16 cycles) and the 16th step (range, 1-20 steps). Of all the procedures, 533 (96.6%) were successfully completed. Compared with the 16-step protocol, the 12-step protocol was associated with an increased BTR risk (odds ratio [OR] 4.05 [95% confidence interval {CI}, 1.7-9.5]; p = 0.001). Multivariate analysis revealed that the BTR risk increased with the total number of RDDs (OR 1.13 [95% CI, 1.0-1.2]; p = 0.026). Skin test positivity was identified as the strongest risk factor for BTRs (OR 2.767 [95% CI, 1.131-6.768]; p = 0.026). Conclusion: Chemotherapy RDD was effective and safe, achieving a 96.6% success rate. The total number of desensitization procedures and skin test positivities were significant predictors of BTRs, indicating that the risk may persist despite successful initial desensitization. Careful risk assessment and close monitoring are essential to ensure patient safety during repeated RDD cycles.