Delving into cornerstones of hypersensitivity to antineoplastic and biological agents: value of diagnostic tools prior to desensitization

• Published in: Allergy (Copenhagen) Vol. 70; no. 7; pp. 784 - 794
• Main Authors: Alvarez‐Cuesta, E., Madrigal‐Burgaleta, R., Angel‐Pereira, D., Ureña‐Tavera, A., Zamora‐Verduga, M., Lopez‐Gonzalez, P., Berges‐Gimeno, M. P.
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.07.2015
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Allergens - administration & dosage; Allergens - adverse effects; Allergies; Antineoplastic Agents - adverse effects; Biological & chemical weapons; Biological Factors - adverse effects; chemotherapy agents; Child; desensitization; Desensitization, Immunologic; Diagnostic tests; Drug Hypersensitivity - diagnosis; Drug Hypersensitivity - etiology; Drug Hypersensitivity - therapy; drug provocation test; Female; Humans; Immunoglobulin E - blood; Immunoglobulin E - immunology; Male; Middle Aged; Organoplatinum Compounds - adverse effects; oxaliplatin; Phenotype; Reproducibility of Results; Sensitivity and Specificity; Severity of Illness Index; Skin Tests; specific IgE; Young Adult; oxaliplatin; chemotherapy agents; specific IgE; drug provocation test; desensitization
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/all.12620

Background Evidence regarding drug provocation test (DPT) with antineoplastic and biological agents is scarce. Our aim was to assess the usefulness of including DPT as a paramount gold standard diagnostic tool (prior to desensitization). Methods Prospective, observational, longitudinal study with patients who, during a 3‐year period, were referred to the Desensitization Program at Ramon y Cajal University Hospital. Patients underwent a structured diagnostic protocol by means of anamnesis, skin tests (ST), risk assessment, and DPT. Oxaliplatin‐specific IgE was determined in oxaliplatin‐reactive patients (who underwent DPT regardless of oxaliplatin‐specific IgE results). Univariate analysis and multivariate analysis were used to identify predictors of the final diagnosis among several variables. Results A total of 186 patients were assessed. A total of 104 (56%) patients underwent DPT. Sixty‐four percent of all DPTs were negative (i.e., hypersensitivity was excluded). Sensitivity for oxaliplatin‐specific IgE (0.35 UI/l cutoff point) was 34%, specificity 90.3%, negative predictive value 45.9%, positive predictive value 85%, negative likelihood ratio 0.7, and positive likelihood ratio 3.5. Conclusions These are the first reported data based on more than 100 DPTs with antineoplastic and biological agents (paclitaxel, oxaliplatin, rituximab, infliximab, irinotecan, and other drugs). Implementation of DPT in diagnostic protocols helps exclude hypersensitivity (in 36% of all referred patients), and avoids unnecessary desensitizations in nonhypersensitive patients (30–56% of patients, depending on culprit‐drug). Drug provocation test is vital to validate diagnostic tools; consequently, quality data are shown on oxaliplatin‐specific IgE and oxaliplatin‐ST in the largest series of oxaliplatin‐reactive patients reported to date (74 oxaliplatin‐reactive patients). Identifying phenotypes and predictors of a diagnosis of hypersensitivity may be helpful for tailored plans.