Elevations in IL-6 Correlate with Cytokine-Related Reactions as a Biomarker for Oxaliplatin Hypersensitivity

Cytokine-Release Reactions (CRRs) are attributed to proinflammatory cytokines such as IL-6 and TNF-α and have been associated to Oxaliplatin hypersensitivity (1-4), with increased serum IL-6 concentrations in the context of fever and rigors (5-6). However, the utility of measuring cytokines such as IL-6 as markers of oxaliplatin hypersensitivity is unknown. We hypothesize that elevations in IL-6 characterize patients experiencing CRRs but not those having Type I hypersensitivity reactions while receiving oxaliplatin for colorectal cancer. A retrospective case review was conducted of 14 oxaliplatin allergic patients who reacted during desensitization at Brigham and Women’s Hospital/Dana Farber Cancer Institute. Data on reaction clinical phenotype was correlated with available serologic biomarkers (Tryptase and IL-6), obtained both at baseline and during hypersensitivity reactions to oxaliplatin. Of the 14 patients, the average baseline tryptase was 6.8ng/mL, (n=6, normal <11.4 ng/ml) and the average baseline IL-6 was 31.5 pg/mL (n=5, normal < 17.4pg/ml). IL-6 was significantly higher on average during CRRs (1242.97pg/mL, n= 16) than during Type I hypersensitivity reactions (70 pg/mL, n=13) p=0.0028. Tryptase was not significantly different between CRR and Type I Reactions (6.24 ng/ml, n=14 and 8.32 ng/mL, n=10 respectively). Elevations in IL-6 correlate well with clinical CRRs to oxaliplatin and help characterize the endotype of such hypersensitivity reactions. IL-6 measurement is useful for the rational modification of future desensitization protocols, since radically different strategies prevent CRRs compared to type I reactions. Monitoring of IL-6 levels may also be relevant for CRRs occurring during treatment with other chemotherapeutics, monoclonal antibodies, and antibiotics.