Endophenotyping Oxaliplatin Hypersensitivity: Personalizing Desensitization to the Atypical Platin

Abstract

Oxaliplatin causes a wider variety of immediate hypersensitivity reactions than do other platin-based chemotherapeutics. Some resemble type 1 reactions that respond to desensitization. Others are atypical, possibly mast cell-independent cytokine release reactions refractory to desensitization. Given this variability, clinicians need an evidence-based strategy to personalize therapy for oxaliplatin-hypersensitive patients. To develop a data-driven algorithm to optimize treatment of oxaliplatin-hypersensitive patients. We retrospectively analyzed the baseline clinical characteristics, biomarkers, and reactions of 48 oxaliplatin-hypersensitive patients who received a total of 266 oxaliplatin desensitizations. We characterized 4 endophenotypes: type 1, cytokine release, mixed, and either. A mean 40-fold increase in serum concentration of IL-6 helped define the cytokine release endophenotype. Younger patients were more likely to have a cytokine release endophenotype, whereas older patients were more likely to have a type 1 reaction. Skin testing was not informative for determining endophenotype or risk of reaction during desensitization, and did not associate with initial or desensitization grade of reaction. Patients with a history of atopy and an initial type 1 reaction responded to desensitization with antihistamine premedications, whereas nonatopic patients with the same initial reaction phenotype were more likely to convert to a cytokine release or mixed reaction during desensitization. We combined these reaction patterns with biomarker data and desensitization outcomes to construct an algorithm that helps tailor desensitization protocol design to meet individual patient needs. Endophenotyping oxaliplatin hypersensitivity reactions may help forecast desensitization outcomes and personalize treatment plans.