Differential presentation of hypersensitivity reactions to carboplatin and oxaliplatin: Phenotypes, endotypes, and management with desensitization

Author:

Jimenez‐Rodriguez Teodorikez‐Wilfox12ORCID,de las Vecillas Leticia34ORCID,Labella Marina256ORCID,Lynch Donna‐Marie7,Besz Kylie Marie7,Marquis Kathleen7,Burgos Amparo8,Soriano Gomis Victor129,Lozano Inmaculada10,Antón Rosa Ana Montoyo11,de la Calle Francisco Marco12,González Delgado María Purificación129,Gutiérrez Aurora3,Montenegro Estefanía3,Rodríguez Fernando3,Fernández Sánchez Francisco Javier129,Castells Mariana7

Affiliation:

1. Allergy Section Dr. Balmis General University Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL) Alicante Spain

2. ARADyAL Spanish Network (RD16/0006) Instituto de Salud Carlos III (ISCIII), Fundación Española para la Ciencia y la Tecnología (FECyT) Madrid Spain

3. Allergy Section Marqués de Valdecilla University Hospital‐IDIVAL Santander Spain

4. Department of Allergy La Paz University Hospital, IdiPAZ Madrid Spain

5. Allergy Clinical Unit Hospital Regional Universitario de Málaga Málaga Spain

6. Allergy Research Group Instituto de Investigación Biomédica de Málaga‐IBIMA Málaga Spain

7. Division of Allergy and Clinical Immunology, Department of Medicine Brigham and Women's Hospital, Harvard Medical School Boston Massachusetts USA

8. Pharmacy Department Dr. Balmis General University Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL) Alicante Spain

9. Department of Clinical Medicine Miguel Hernández University Alicante Spain

10. Oncology Section Dr. Balmis General University Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL) Alicante Spain

11. Oncology Day Hospital Nursing Service Dr. Balmis General University Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL) Alicante Spain

12. Immunology Section Dr. Balmis General University Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL) Alicante Spain

Abstract

AbstractBackgroundDrug hypersensitivity reactions (DHRs) to platinum‐based drugs are heterogenous and restrict their access, and drug desensitization (DD) has provided a ground‐breaking procedure for their re‐introduction, although the response is heterogeneous. We aimed to identify the phenotypes, endotypes, and biomarkers of reactions to carboplatin and oxaliplatin and their response to DD.MethodsSeventy‐nine patients presenting with DHRs to oxaliplatin (N = 46) and carboplatin (N = 33) were evaluated at the Allergy Departments of two tertiary care hospitals in Spain. Patient symptoms, skin testing, biomarkers, and outcomes of 267 DDs were retrospectively analyzed.ResultsOxaliplatin‐reactive patients presented with type I (74%), cytokine release reaction (CRR) (11%), and mixed (Mx) (15%) phenotypes. In contrast, carboplatin reactive patients presented with predominantly type I (85%) and Mx (15%) but no CRRs. Out of 267 DDs, breakthrough reactions (BTRs) to oxaliplatin occurred twice as frequently as carboplatin (32% vs. 15%; p < .05). Phenotype switching from type I to another phenotype was observed in 46% of oxaliplatin DDs compared to 21% of carboplatin DDs. Tryptase was elevated in type I and Mx reactions, and IL‐6 in CRR and Mx, indicating different mechanisms and endotypes.ConclusionCarboplatin and oxaliplatin induced three different types of reactions with defined phenotypes and endotypes amendable to DD. Although most of the initial reactions for both were type I, oxaliplatin presented with unique CRR reactions. During DD, carboplatin reactive patients presented mostly type I BTR, while oxaliplatin‐reactive patients frequently switched from type I to CRR, providing a critical difference and the need for personalized DD protocols.

Publisher

Wiley

Subject

Immunology,Immunology and Allergy

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