Oxaliplatin-Induced Type II Hypersensitivity in Colorectal Cancer: A Cohort Study on Clinical Presentation, Diagnosis, and Management

Paula Vazquez-Revuelta^1,2,3,4*Ricardo Madrigal-Burgaleta⁵J. Carlos Ruffinelli⁶Enric Casanovas⁷Ana Coloma⁸Ramon Lleonart²

• ¹Drug Hypersensitivity and Desensitization Centre (DHDC), Institut Català d’Oncologia (ICO), Barcelona, Spain
• ²Allergy Department, Hospital Universitari de Bellvitge (HUB), Barcelona, Spain
• ³Institut d'Investigacio Biomedica de Bellvitge (IDIBELL), Barcelona, Catalonia, Spain
• ⁴University of Barcelona, Barcelona, Catalonia, Spain
• ⁵Allergy & Severe Asthma Service, St Bartholomew's Hospital, Barts Health NHS Trust, London, United Kingdom
• ⁶Medical Oncology Department, Institut Català d’Oncologia (ICO), Barcelona, Spain
• ⁷Immunohaemathology Laboratory, Banc de Sang I Teixits, Barcelona, Spain
• ⁸Nephrology Department, Hospital Universitari de Bellvitge (HUB), Barcelona, Spain

Background: Oxaliplatin (OXL) is a key treatment for colorectal cancer but can potentially induce type II hypersensitivity reactions (II-HSRs), leading to immune-mediated cytopenias. The prevalence and management of OXL-induced II-HSRs remain poorly understood, with evidence being mainly anecdotal and lacking a systematic approach. This study examines the prevalence, clinical presentation, diagnosis, and management of OXL-induced II-HSRs in our population. Methods: We retrospectively analysed a cohort of OXL-reactive patients at our Drug Hypersensitivity and Desensitisation Centre between January 2019 and April 2024. Patients with clinical and laboratory findings suggestive of II-HSR were included and classified into acute immune thrombocytopenia (AIT), immune haemolytic anaemia (IHA), Evans syndrome (ES), or drug-induced thrombotic microangiopathy (DITMA). Drug-dependent antibodies (DDAbs) were detected via flow cytometry. Carefully selected patients underwent re-exposure to OXL under allergy care and special safety measures. Results: Sixteen patients were diagnosed with II-HSRs, with a prevalence of 9.5% among OXL-reactive patients. The mean number of OXL cycles at onset was 20. Atypical hypersensitivity symptoms such as chills, fever, and back pain aided clinical identification. AIT was most common (56%), followed by ES (38%), and one case of DITMA (6%). DDAbs were detected in 86% of cases, with two patients showing DDAbs to other drugs. Five selected patients were re-exposed to OXL without significant complications. Conclusions: OXL-induced II-HSRs are rare but pose diagnostic and management challenges. This study shows the importance of early identification, the potential role of DDAbs testing, and the feasibility of re-exposure under controlled conditions in selected patients.