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TRYPTASE AND IL-6: ROLE OF BIOMARKERS DURING HYPERSENSITIVITY REACTIONS
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Journal Article
TRYPTASE AND IL-6: ROLE OF BIOMARKERS DURING HYPERSENSITIVITY REACTIONS
2025
Overview
Significance & Background: Drug hypersensitivity reactions (HSRs) impact patient cancer treatments and outcomes. These reactions can be defined by their clinical presentation (phenotypes), pathophysiology (endotype), and biomarkers. For patients undergoing rapid desensitization (RDD), biomarkers such as skin testing, serum tryptase, and serum lnterleukin (IL)-6 levels can be used to guide protocol selection (both initial and subsequent if continued reactions) and clinical outcomes. Purpose: To develop a RDD treatment algorithm based on the initial and breakthrough HSR phenotypes and associated biomarkers in patients referred to the Brigham and Women's Hospital Drug Desensitization Center. Methods: This study was a retrospective IRB-approved descriptive analysis of adult patients from January 2022 through August 2023. Data collected included symptom presentation, desensitization protocols/outcomes and the following associated biomarkers: skin test, tryptase, and IL-6 levels at the initial reaction and during breakthrough desensitization reactions (BTRs). Interventions: Patients were classified into 3 groups based on endophenotype (Type 1, Cytokine Release Reactions (CRR), and Mixed). Positive skin testing and/or elevated tryptase levels with only symptoms of Type 1 HSR were provided multiple bag desensitization protocols. Patients with an elevated IL-6 that only experienced CRR symptoms were provided a 1 bag protocol. Patients that experienced mixed reactions symptoms of both CRR and Type 1 and/or positive biomarkers received multiple bag protocols. Results: A total of 1,633 desensitization protocols were provided to 326 patients. Biomarkers obtained included skin testing (242 patients), initial reaction tryptase levels (185 patients), BTR tryptase levels (154 patients), initial reaction IL-6 levels (35 patients), and BTR IL-6 levels (142 patients). Based on biomarkers specific desensitization protocols were administered, 4 bag / 16 step (30), 3 bag / 12 step (835), 2 bag / 8 step (327), 1 bag /4-6 step (356) and 1 bag challenges (85). There were 87% protocols (1423) were completed without reactions and 13% with mild to moderate reactions, without deaths. Of the 228/1633 (14%) desensitization protocols completed in patients with an initial CRR phenotype, 208 (91.2%) were successfully completed without reactions. Discussion: Defining the pathogenic mechanism of HSRs helps select specific desensitization protocols (number of bags, steps, and premedication), which increases safety upon re-exposure. The application of biomarkers, although useful in understanding HSR phenotype and endotypes, may have an even greater impact when used to predict response or modify treatment in the setting of desensitization to targeted therpies.
Publisher
Oncology Nursing Society
Subject
