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  • 683 Endophenotyping of carboplatin hypersensitivity reactions in patients with gynecologic and breast malignancies and changes during drug desensitization

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05. Miscellaneous
683 Endophenotyping of carboplatin hypersensitivity reactions in patients with gynecologic and breast malignancies and changes during drug desensitization
  1. Teodorikez Wilfox Jimenez-Rodriguez1,2,
  2. Inmaculada Lozano Cubo3,
  3. Adrián Viudez-Martínez4,
  4. Lucia Gómez-González3,
  5. Victor Soriano-Gomis1,2,5,
  6. María Purificación González-Delgado1,2,5,
  7. Rosa Ana Montoyo-Antón6,7,
  8. Montserrat García-Araque7,
  9. Elena Peña Zurdo7,
  10. Daniel Parra Trujillo3,
  11. Guillermo Forner Cuenca3,
  12. María José Roman-Sánchez8,
  13. Manuela Sala Ferichola8,
  14. Josefa Marcos Sanmartin8 and
  15. Amparo Burgos San José4
  1. 1Allergy Section, Dr. Balmis General University Hospital; Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain
  2. 2ARADyAL Spanish Network (RD16/0006). Instituto de Salud Carlos III (ISCIII). Fundación Española para la Ciencia y la Tecnología (FECyT), Madrid, Spain
  3. 3Oncology Department, Dr. Balmis General University Hospital; Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain
  4. 4Pharmacy Department, Dr. Balmis General University Hospital; Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain
  5. 5Department of Clinical Medicine, Miguel Hernández University, ISABIAL, Alicante, Spain
  6. 6Oncology Day Hospital Nursing Service, Dr. Balmis General University Hospital; Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain
  7. 7Oncology Clinical Trials Unit, Dr. Balmis General University Hospital; Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain
  8. 8Gynecology and obstetrics Department, Dr. Balmis General University Hospital; Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain

Abstract

Introduction/Background Gynecological and breast neoplasms have a high incidence. The use of more than 7 doses of carboplatin is the main risk factor for developing hypersensitivity reactions (HSRs). HSRs are divided into immediate (IHSR) and non-immediate (NIHSR). IHSRs, can be of different phenotypes: type I (IgE or non-IgE mediated), cytokine release reactions (CRR), mixed (Mx) or indeterminate (Id). Precision medicine, has made it possible endophenotype carboplatin-induced reactions, which has been useful to predict the reappearance of HSRs after its reintroduction, as well as patient’s response to drug desensitization (DD).

Methodology Between January 2018 and June 2023, forty-three patients diagnosed with gynecological and breast neoplasms: 32 ovarian, 6 endometrial, 2 breast, 1 cervix, and with double neoplasia 2 ovarian/cervix, 1 ovarian/urothelial, and 1 cervix/endometrial, were sent to the Allergy Section of the Dr. Balmis General University Hospital, Alicante-Spain, due to HSR to carboplatin. Patient symptoms, skin testing, biomarkers, and outcomes of 194 DDs were retrospectively analyzed.

Results Ninety-one percent (n=39) of carboplatin-reactive patients had IHSRs and 9% (n=4) had NIHSRs that, after repeated exposures, led to IHSRs (converter phenotype). IHSRs from both groups were phenotyped in type I (79%) and Mx (21%) reactions, no CRR were observed. Out of 194 DDs, breakthrough reactions (BTRs) occurred during 35 protocols (23%). Phenotype switching from type I to another phenotype (Mx or NIHSRs) was observed in 14%, and from Mx to type I in 3% of BTRs (p< 0.01). Tryptase was elevated in type I, and tryptase and IL-6 in Mx reactions, indicating different mechanisms and endotypes.

Conclusion Carboplatin induces mainly type I reactions. Other phenotypes are rare to observe, but all of them respond adequately to DD.

Phenotypes may change during DD, from type I to Mx or NIHSR, so customizing DD protocols is necessary to maintain patient safety.

Disclosures None of the authors have a conflict of interest related to this presentation.

https://doi.org/10.1136/ijgc-2024-ESGO.517

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