Abstract
Introduction: Phenotype I hypersensitivity reactions are the most commonly reported drug reactions; however, precision medicine has made it possible to characterize new phenotypes. A recent communication proposed the existence of a “converter phenotype,” which would affect patients who present non-immediate hypersensitivity reactions and in subsequent exposures develop immediate hypersensitivity reactions. This study aimed to describe the clinical characteristics of converter phenotype reactions and their evolution during desensitization to chemotherapeutic drugs and monoclonal antibodies.Methods: We retrospectively reviewed our database of patients undergoing desensitization to chemotherapy or biological agents and selected those with a converter phenotype. Demographic and clinical characteristics of the patients, the results of skin tests, tryptase and IL-6 levels, and desensitization outcomes were assessed.Results: Of 116 patients evaluated, 12 (10.3%) were identified as having a converter phenotype. The median interval between drug exposure and reaction was 90.6 h (range 8-288 h). After the conversion, phenotype I was the most frequent (58.3%), followed by cytokine release reactions (33.3%). Fifty-one desensitizations were undertaken and all treatments completed, with 10 (19.6%) breakthrough reactions. No new changes in the phenotype were detected.Conclusions: The symptoms of non-immediate drug hypersensitivity reactions may indicate the need for an early allergological evaluation to assess the risk of future immediate drug reactions. Clinical characteristics, skin test results, and biomarkers can help predict responses to rapid drug desensitization, guiding clinicians on how to optimize therapy delivery while maintaining patient safety.
Highlights
Phenotype I hypersensitivity reactions are the most commonly reported drug reactions; precision medicine has made it possible to characterize new phenotypes
Of the 116 patients evaluated for drug hypersensitivity reactions (DHR) to chemotherapeutic and biological drugs, 12 (10.3%) met criteria for converter phenotype” (CPh): 3 (25%) had reactions to paclitaxel, 3 (25%) to docetaxel, 2 (16.7%) to rituximab, 1 (8.3%) to adalimumab, 1 (8.3%) to brentuximab, 1 (8.3%) to carboplatin, and 1 (8.3%) to oxaliplatin
Patients reacting to taxanes had the least historical exposure to these drugs (83.3% had a reaction on their first exposure), while the carboplatin-allergic patient had been the most exposed (16 previous exposures prior to DHR)
Summary
Phenotype I hypersensitivity reactions are the most commonly reported drug reactions; precision medicine has made it possible to characterize new phenotypes. Phenotype I (PhI) reactions are the most commonly reported kinds of drug hypersensitivity reactions (DHR) according to the Gell and Coombs’ classic description; precision medicine has brought to light other types that had no place into this classification, such as cytokine release reactions [1]. Gell and Coombs’ classification left out some phenotypes of nonimmediate drug hypersensitivity reactions (NIDHR), including accelerated reactions [2, 3]. The so-called the “converter phenotype” (CPh) defined a group of taxane-treated patients who initially presented with NIDHRs but developed IDHRs after subsequent exposures, generally PhI reactions [6]
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