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Differential presentation of hypersensitivity reactions to carboplatin and oxaliplatin: phenotypes, endotypes and management with desensitization.
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  • Teodorikez Jimenez-Rodriguez,
  • Leticia De las Vecillas Sánchez,
  • Marina Labella,
  • Donna-Marie Lynch,
  • Kylie Marie Besz,
  • Kathleen Marquis,
  • Amparo Burgos,
  • Victor Soriano Gomis,
  • Inmaculada Lozano,
  • Rosa Ana Montoyo Antón,
  • Francisco Marco de la Calle,
  • Purificacion Gonzalez Delgado,
  • Aurora Gutiérrez,
  • Estefanía Montenegro,
  • Fernando Rodríguez,
  • Javier Fernandez,
  • Mariana Castells
Teodorikez Jimenez-Rodriguez
Dr Balmis General University Hospital Alicante Institute for Health and Biomedical Research (ISABIAL
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Leticia De las Vecillas Sánchez
Hospital Universitario Marques de Valdecilla
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Marina Labella
ARADyAL Spanish Network (RD16/0006
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Donna-Marie Lynch
Brigham and Women’s Hospital Harvard Medical School
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Kylie Marie Besz
Brigham and Women’s Hospital Harvard Medical School
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Kathleen Marquis
Brigham and Women’s Hospital Harvard Medical School
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Amparo Burgos
Dr Balmis General University Hospital Alicante Institute for Health and Biomedical Research (ISABIAL
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Victor Soriano Gomis
Dr Balmis General University Hospital Alicante Institute for Health and Biomedical Research (ISABIAL
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Inmaculada Lozano
Dr Balmis General University Hospital Alicante Institute for Health and Biomedical Research (ISABIAL
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Rosa Ana Montoyo Antón
Dr Balmis General University Hospital Alicante Institute for Health and Biomedical Research (ISABIAL
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Francisco Marco de la Calle
Dr Balmis General University Hospital Alicante Institute for Health and Biomedical Research (ISABIAL
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Purificacion Gonzalez Delgado
Dr Balmis General University Hospital Alicante Institute for Health and Biomedical Research (ISABIAL
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Aurora Gutiérrez
Hospital Universitario Marques de Valdecilla
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Estefanía Montenegro
Hospital Universitario Marques de Valdecilla
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Fernando Rodríguez
Hospital Universitario Marques de Valdecilla
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Javier Fernandez
Dr Balmis General University Hospital Alicante Institute for Health and Biomedical Research (ISABIAL
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Mariana Castells
Brigham and Women’s Hospital Harvard Medical School

Corresponding Author:[email protected]

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Abstract

Background Drug 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. Methods Seventy-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. Results Oxaliplatin-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% versus 15%; p<0.05). 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. Conclusion Carboplatin 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.
15 Aug 2023Submitted to Allergy
16 Aug 2023Submission Checks Completed
16 Aug 2023Assigned to Editor
16 Aug 2023Review(s) Completed, Editorial Evaluation Pending
18 Aug 2023Reviewer(s) Assigned
04 Sep 2023Editorial Decision: Revise Minor
18 Oct 20231st Revision Received
18 Oct 2023Review(s) Completed, Editorial Evaluation Pending
18 Oct 2023Submission Checks Completed
18 Oct 2023Assigned to Editor
21 Oct 2023Editorial Decision: Accept