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.

Mauro Pagani

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Chemotherapeutic drugs have been widely used in the treatment of cancer disease for about 70 years and, even with the development of new therapies, they are still prescribed by oncologists, alone or in combination with other antineoplastic agents. All chemotherapies are able to provoke hypersensitivity reactions, even with different incidences, depending on the different class of these drugs, and these reactions are the third leading cause of fatal drug-induced anaphylaxis in the United States. In Europe deaths related to chemotherapy have also been reported. In particular, most reactions are provoked by platinum compounds, taxanes, epipodophyllotoxins and asparaginase. However, currently there are different points of view about the best procedures for the diagnosis, treatment and prevention of these reactions. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology organized a task force to provide data and recommendations regarding the allergological work up in this field of drug hypersensitivity reactions. The aims of this position paper were to provide consensus on the investigation of HSRs to chemotherapeutic drugs and to give practical suggestions for clinicians that treat these patients, such as oncologists, allergologists and internists. Key sections cover: risk factors, pathogenesis, symptoms, role of skin tests, in vitro tests, indications and contraindications of drug provocation tests and desensitization of neoplastic patients with allergic reactions to chemotherapeutic drugs. Statements, recommendations and unmet needs were discussed and proposed at the end of each section.

Denisa Ferastraoaru

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