Converter Phenotype: A New Profile That Is Not Exclusive to Taxanes

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.

Serum tryptase and drug hypersensitivity: why, how and what? A systematic review

“…Other forms of immediate drug hypersensitivity have been described, most notably the cytokine release syndrome, which is not related to mast cell activation [7]. In this case, serum tryptase does not exhibit the typical transient increase and provides only indirect diagnostic evidence, that is lack of evidence for a mast cell-induced mechanism, while cytokine biomarkers, such as serum IL-6, help identify an endotype-phenotype connection and hold promising diagnostic performance [ 4]. The main differences between mast cell-induced hypersensitivity and cytokine release or infusion reaction are presented in Fig.…”

“…mast cell mediated) and nonimmediate hypersensitivity (e.g. T lymphocyte-mediated delayed skin reactions) [3 ▪▪ ,4,5,6 ▪ ]. The connection between endotype and phenotype is increasingly recognized, with the most recent classifications providing guidance for multiple clinical and biomarker pictures of drug hypersensitivity [7].…”

“…A combination of clinical and biomarker scoring also help identify nonmast cell-related immediate drug hypersensitivity, such as during drug hypersensitivity episodes with IL-6-related cytokine release syndromes [ ]. Together with mast cell-induced immediate drug hypersensitivity, cytokine release syndrome also contributes to the converter phenotype, that is transitioning from delayed to immediate drug hypersensitivity, underscoring the need for timely allergy investigation of delayed drug hypersensitivity reactions [4].…”

“…In this case, serum tryptase does not exhibit the typical transient increase and provides only indirect diagnostic evidence, that is lack of evidence for a mast cell-induced mechanism, while cytokine biomarkers, such as serum IL-6, help identify an endotype–phenotype connection and hold promising diagnostic performance [6 ▪ ,12 ▪▪ ]. Mixed phenotypes with concomitant raise in serum tryptase and serum IL-6 are also described [3 ▪▪ ,4]. The main differences between mast cell-induced hypersensitivity and cytokine release or infusion reaction are presented in Fig.…”

“…Fever and a transient increase in serum IL-6 but not in serum tryptase were the best predictors for drug hypersensitivity presenting as breakthrough reactions during rapid desensitization to chemotherapy and biologicals [6 ▪ ]. Together with mast cell-induced immediate drug hypersensitivity, cytokine release syndrome also contributes to the converter phenotype, that is transitioning from delayed to immediate drug hypersensitivity, underscoring the need for timely allergy investigation of delayed drug hypersensitivity reactions [4].…”