A New Successful Rapid Desensitization Protocol for Hypersensitivity Reactions to Carboplatin and Rituximab in the Pediatric Setting

Introduction

Hypersensitivity reactions (HSRs) can be induced by many medications, including chemotherapy agents and monoclonal antibodies (mAbs). Virtually all chemotherapeutics have the potential to initiate infusion reactions. Allergies to chemotherapeutics and biologic agents usually manifest with skin symptoms (rash, itching, and swelling), angioedema, or even potentially fatal anaphylactic reactions. Medication allergies may lead to discontinuation of life-prolonging therapies and therefore worsen prognosis. For clinical situations where hypersensitivity reactions prevent administration of a critical medication, desensitization can be an extremely useful addition to the clinical toolkit. In the early 2000s, multiple clinical trials showed that Rapid Drug Desensitization (RDD) for chemotherapy and mAbs was safe and effective in improving clinical outcomes and allowing patients to remain on preferred first-line therapy.

Desensitization is challenging however, and this is reflected in variable success rates reported in the literature. One recent review noted successful desensitization in anywhere from 20 to 75% of cases (Ruggiero et al. 2017). This wide range is likely due to different methods of desensitization used in various studies. There are multiple variables influencing the success of desensitization, including the starting dose, the infusion rate, and the number of increments. Desensitization protocols are often complex requiring multiple changes in the rate and volume of medication administered between steps--making it difficult to complete them correctly. We have developed a new, simpler desensitization method that does not require multiple changes in the infusion rate and volume, thus reducing clinical confusion and leading to improved patient outcomes.

Methods

We developed a standardized protocol for rapid desensitization in patients who had hypersensitivity reactions to carboplatin or rituximab. This new desensitization method utilizes the same rate, administration time, and volume for each dose, only changing the drug concentration gradually between steps. This method helps minimize the chance of errors that occur due to repeatedly reprogramming the rate and volume of the infusion.

A total of 10 patients were treated under this desensitization protocol between November 2017 and June 2020 for a total of 76 desensitization episodes. Initial desensitization occurred in the medical intensive care unit and subsequent infusions of carboplatin took place in an outpatient hematology-oncology setting. We retrospectively analyzed safety and efficacy of this novel desensitization protocol through review of treatment records.

Results

Of the 76 desensitizations performed, no adverse reactions occurred during desensitization and patients received their full target dose in all cases. No breakthrough reactions were noted during subsequent infusions of carboplatin or rituximab in desensitized patients. To prevent breakthrough reactions, antihistamines, corticosteroids and a leukotriene modifier were administered as pre-medications. Patients undergoing carboplatin desensitization were able to be switched from a 12-step protocol to a 10-step protocol with the same 100 % success rate in completing the entire planned cycle of chemotherapy.

Discussion

This retrospective analysis demonstrated a statistically and clinically significant reduced rate of breakthrough reactions in comparison to previous reports (Brennan et al. 2009). The other benefits of this novel method include improvement in safety of administration and cost savings.