Clinical characteristics and genetic HLA marker for patients with oxaliplatin-induced adverse drug reactions

Hung-Chih Hsu; Wen-Hung Chung; Yung-Chang Lin; Tsai-Sheng Yang; John Wen-Cheng Chang; Chia-Hsun Hsieh; Shuen-Iu Hung; Chun-Wei Lu; Jen-Shi Chen; Wen-Chi Chou; Chuang-Wei Wang

Allergology International (Oct 2024)

Clinical characteristics and genetic HLA marker for patients with oxaliplatin-induced adverse drug reactions

Hung-Chih Hsu,
Wen-Hung Chung,
Yung-Chang Lin,
Tsai-Sheng Yang,
John Wen-Cheng Chang,
Chia-Hsun Hsieh,
Shuen-Iu Hung,
Chun-Wei Lu,
Jen-Shi Chen,
Wen-Chi Chou,
Chuang-Wei Wang

Affiliations

Hung-Chih Hsu: Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
Wen-Hung Chung: College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan; Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Taiwan; Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China; Cancer Vaccine and Immune Cell Therapy Core Laboratory, Department of Medical Research, Chang Gung Memorial Hospital, Linkou, Taiwan; Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan; Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Dermatology, Beijing Tsinghua Chang Gung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China; Department of Dermatology, Ruijin Hospital, Shanghai, China; School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Yung-Chang Lin: Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
Tsai-Sheng Yang: Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
John Wen-Cheng Chang: Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan
Chia-Hsun Hsieh: Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
Shuen-Iu Hung: Cancer Vaccine and Immune Cell Therapy Core Laboratory, Department of Medical Research, Chang Gung Memorial Hospital, Linkou, Taiwan; Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taiwan
Chun-Wei Lu: College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan; Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Taiwan; Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China
Jen-Shi Chen: Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
Wen-Chi Chou: Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
Chuang-Wei Wang: Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan; Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Taiwan; Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China; Cancer Vaccine and Immune Cell Therapy Core Laboratory, Department of Medical Research, Chang Gung Memorial Hospital, Linkou, Taiwan; Corresponding author. Department of Dermatology, Drug Hypersensitivity Clinical and Research Center; Cancer Vaccine and Immune Cell Therapy Core Laboratory, Department of Medical Research, Chang Gung Memorial Hospital, Linkou, No. 5, Fusing St, Taoyuan 333, Taiwan.

Journal volume & issue: Vol. 73, no. 4
pp. 580 – 586

Abstract

Read online

Background: Oxaliplatin is commonly used to treat gastrointestinal malignancies. However, its applications are limited due to potential adverse drug reactions (ADRs), particularly severe anaphylactic shock. There is no method to predict or prevent ADRs caused by oxaliplatin. Therefore, we aimed to investigate the genetic HLA predisposition and immune mechanism of oxaliplatin-induced ADRs. Methods: A retrospective review was performed for 154 patients with ADRs induced by oxaliplatin during 2016–2021 recorded in our ADR notification system. HLA genotyping was conducted for 47 patients with oxaliplatin-induced ADRs, 1100 general population controls, and 34 oxaliplatin-tolerant controls in 2019–2023. The in vitro basophil activation test (BAT) was performed and oxaliplatin-specific IgE levels were determined. Results: The incidence of oxaliplatin-induced ADRs and anaphylactic shock in our cohort was 7.1% and 0.15%, respectively. Of the 154 patients, 67.5% suffered rash/eruption; 26.0% of the patients who could not undergo oxaliplatin rechallenge were considered to show oxaliplatin-induced immune-mediated hypersensitivity reactions (HRs). The genetic study found that the HLA-DRB∗12:01 allele was associated with oxaliplatin-induced HRs compared to the general population controls (sensitivity = 42.9%; odds ratio [OR] = 3.4; 95% CI = 1.4–8.2; P = 0.008) and tolerant controls (OR = 12; 95% CI = 2.3–63.7; P = 0.001). The in vitro BAT showed higher activation of CD63+ basophils in patients with oxaliplatin-induced HRs compared to the tolerant controls (P < 0.05). Only four patients (8.5%) with oxaliplatin-induced ADRs were positive for oxaliplatin-specific IgE. Conclusions: This study found that 26.0% of patients with oxaliplatin-induced ADRs could not undergo oxaliplatin rechallenge. HLA-DRB∗12:01 is regarded as a genetic marker for oxaliplatin-induced hypersensitivity.

Published in Allergology International

ISSN: 1323-8930 (Print); 1440-1592 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: https://www.journals.elsevier.com/allergology-international/

About the journal

Abstract

Keywords