Jared Silver1, Marlene Garcia-Neuer2, Donna-Marie Lynch1, Gülden Pasaoglu3, David E Sloane4, Marianna Castells1. 1. Division of Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. 2. The Ohio State University College of Medicine, Columbus, Ohio. 3. Department of Adult Immunology-Allergy, Florence Nightingale Hospitals, Kadıkoy Medicine Center, Istanbul, Turkey. 4. Division of Allergy and Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. Electronic address: dsloane@bwh.harvard.edu.
Abstract
BACKGROUND: 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. OBJECTIVE: To develop a data-driven algorithm to optimize treatment of oxaliplatin-hypersensitive patients. METHODS: We retrospectively analyzed the baseline clinical characteristics, biomarkers, and reactions of 48 oxaliplatin-hypersensitive patients who received a total of 266 oxaliplatin desensitizations. RESULTS: 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. CONCLUSIONS: Endophenotyping oxaliplatin hypersensitivity reactions may help forecast desensitization outcomes and personalize treatment plans. Published by Elsevier Inc.
BACKGROUND: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-hypersensitivepatients. OBJECTIVE: To develop a data-driven algorithm to optimize treatment of oxaliplatin-hypersensitivepatients. METHODS: We retrospectively analyzed the baseline clinical characteristics, biomarkers, and reactions of 48 oxaliplatin-hypersensitivepatients who received a total of 266 oxaliplatin desensitizations. RESULTS: 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. CONCLUSIONS: Endophenotyping oxaliplatinhypersensitivity reactions may help forecast desensitization outcomes and personalize treatment plans. Published by Elsevier Inc.
Authors: Teodorikez Wilfox Jimenez-Rodriguez; Francisco Manuel Marco de la Calle; Inmaculada Lozano-Cubo; Rosa Ana Montoyo-Anton; Victor Soriano-Gomis; Purificación Gonzalez-Delgado; Amparo Burgos-San José; Seira Climent-Ballester; Natividad Martínez-Banaclocha; Javier Fernández-Sanchez Journal: Front Allergy Date: 2022-01-12
Authors: Hyun Hwa Kim; Jeongmin Seo; Yoon Hae Ahn; Hyunjee Kim; Jeong-Eun Yoon; Jang Ho Suh; Dong Yoon Kang; Suh Young Lee; Hye-Ryun Kang Journal: Front Allergy Date: 2022-02-11
Authors: James H Lewis; Sophia K Khaldoyanidi; Carolyn D Britten; Andrew H Wei; Marion Subklewe Journal: Am J Clin Oncol Date: 2022-07-18 Impact factor: 2.787