Interleukin‐6: A novel biomarker for monoclonal antibody and chemotherapy‐associated hypersensitivity confirms a cytokine release syndrome phenotype‐endotype association

Hypersensitivity Reactions to Cancer Chemotherapy: Practical Recommendations of ARADyAL for Diagnosis and Desensitization

“…Cytokines maximum levels are found around 100 minutes after the reaction onset and sustained for as long as 10 hours [82]. IL-6 is proposed as a biomarker of CRR [14,87].…”

Hypersensitivity reactions and anaphylaxis to checkpoint inhibitor–monoclonal antibodies and desensitization

“…[29][30][31][32][33][34][35] Tryptase can be elevated in type I HRs but also in mixed reactions along with interleukin (IL)-6 biomarker when cytokine release is associated. 24,25,36,37 A novel study, recently published by Jakubovic et al, 37 has explored IL-6 as a biomarker for breakthrough reactions during DD to chemotherapeutics and mabs. Of 21 patients, 38 reactions were evaluated to determine the phenotypic constellations with which elevated values of IL-6 may correlate.…”

“…This observation may indicate that although DD is thought to prevent mast cell mediator release, the source of IL-6 is likely from other immune cells and DD may not block all pathways of anaphylaxis. 37…”

Medical algorithm: Diagnosis and treatment of hypersensitivity reactions to cancer chemotherapy

“…10 Patients amenable to RDD are classified according to their clinical presentation and biomarkers into an 'endophenotype', namely, type I (mast cell-/basophil-mediated, whether IgE-dependent or not, and can be associated with elevated tryptase), cytokine-release reaction (CRR, with fever/chills, malaise, flushing, hypotension, and can be associated with elevated IL-6), mixed reaction (features of both type I and CRR) or non-severe type-IV reaction. 10,13 ST is an extremely useful tool, however, not all drugs are available for ST, while for those with the option of ST, concentrations and methodology are heterogeneous, which makes comparisons between different groups challenging. 3,4 There is a difficult balance between prioritising sensitivity and specificity, namely, excessive dilution can potentially affect stability and/or reactivity (false-negatives), while insufficient dilution has shown to cause burns or false-positives.…”

“…4,9 However, ST is an essential tool in the risk-assessment before delabelling and RDD, 3,4 with even one group basing their management pathways of DHRs to platins in repeated ST. 14 The role of in vitro testing might be still limited in DHRs to chemotherapy, but tryptase can be used to detect basophil/mast cell mediator release, whereas IL6 to detect cytokine release. 1,4,13 Alvarez-Cuesta et al 2 validated specific IgE (sIgE) to oxaliplatin in a large cohort of well-characterised patients, finding that this technique was very specific but not so sensitive. However, excluding patients with a CRR endophenotype from the analysis of the data available in the said study could potentially improve sensitivity.…”