Rapid drug desensitization with platin-based chemotherapy: Analysis of risk factors for breakthrough reactions

Background: All platin-based chemotherapeutics can cause hypersensitivity reactions (HSRs). With rapid drug desensitization (RDD), few patients experience breakthrough reactions (BTR) during desensitization. However, data about risk factors for BTRs during RDD in patients with HSRs to platins are limited. We first aimed to describe characteristics of our platin-reactive population and to validate the Brigham and Women's Hospital's (BWH's) RDD protocol in our population along with their outcomes with RDD. Our second aim was to identify the risk factors for BTRs. Method: This was a retrospective chart review (2013-2020) of patients with symptoms of immediate HSRs to platins. Initial HSRs were classified as grade 1, 2, or 3 based on their severity. Skin prick tests (SPT)/intradermal tests (IDT) were performed with implicated platins. A 12-step protocol was used during RDD. Results: The study comprised 65 women and seven men (mean age 57.78 +/- 8.73 years). Initial HSRs to carboplatin, cisplatin, and oxaliplatin occurred in 38, 13, and 21 patients, respectively. All patients reacted at the fifth (median) recurrent infusions (min:1, max:20). The median values for carboplatin, cisplatin, and oxaliplatin were 6 (1-20), 3 (1-15), and 3 (1-11), respectively. Most initial HSRs were grade 2 (n = 40, 55.6%) and 3 (n = 27, 37.5%); only 6.9% (n = 5) were grade 1. Patients with grade 1, 2, and 3 initial HSRs had positive platin skin test results at rates of 80%, 74%, and 88%, respectively. A total of 232 RDDs were performed in 72 patients and 98.7% of these desensitizations were completed. BTRs occurred in 56 (24.1%) (grade 1 n = 14, 25%; grade 2 n = 32, 57%; grade 3 n = 10, 18%) of these desensitizations. Breakthrough reactions were more severe in patients with positive SPTs or 1:100 or 1:10 dilutions of IDT (p = 0.014). BTR was not observed during RDD in any of the patients with positive 1:1 dilutions of IDT. Positivity on prick or 1:100 or 1:10 IDT increased the risk of BTR 5.058 times. There was no significant association between the risk of BTRs and age, drug cycle, sex, comorbidities, or atopy. Conclusion: In our experience, 98.7% of 232 RDDs to platins were completed successfully, showing that RDD was safe and effective. Drug skin test positivity is a potential marker for identifying high-risk patients who will have BTRs during RDDs to platins.