Severe first infusion reaction related to cetuximab in cancer patients in Arkansas

Abstract

Introduction Cetuximab, a chimeric monoclonal antibody, is a commonly used anticancer drug that prevents binding of epidermal growth factor to epidermal growth factor receptor. It has been widely used in a variety of cancers since its initial approval by the FDA in 2004. Despite its efficacy, it has met with some genuine concerns especially regarding the anaphylactoid reactions occurring after first infusions. Cetuximab-related first infusion reaction has been found to be much more prevalent in the Southeastern United States with several studies from the southern United States supporting it. The purpose of our study was to determine the rate of first infusion reaction in the state of Arkansas and the factors that could predispose to first infusion reaction. Methods and results We performed a retrospective chart review of consecutive patients who received cetuximab between January 2004 and December 2016 at the University of Arkansas for Medical Sciences. We included a total of 220 patients in our analysis out of which 32 (14.5%) developed cetuximab-related first infusion reaction. There was a statistically significant increased risk in males versus females (18.2% vs. 8.4%, P = 0.045) and trend toward significance for the difference between Caucasians and Blacks (16.5% vs. 7.1%, P = 0.054). Conclusion There is increased incidence of cetuximab-related first infusion reaction in Arkansas which is much higher than the national average but comparable to the incidence in other neighboring states in the Southeastern United States. This increased incidence tends to cluster in Caucasian males. Safer alternatives should be preferred for treatment of cancers particularly in the Southeastern United States whenever possible.

Subvisible Particles in IVIg Formulations Activate Complement in Human Serum

“…Particle concentrations and images of particles in the various stressed formulations were obtained using flow imaging microscopy (FlowCAM®, Fluid Imaging Technologies, Scarborough, ME), as previously described. 15 Samples that had been subjected to 6 freeze-thaw cycles contained concentrations of particles that approached or exceeded the upper limit for the flow imaging microscopy instrument, and so these formulations were diluted 100fold with PBS, pH 7.4, before analysis. Particle counts in the stressed formulations were measured in aliquots that were sampled from the same individual syringes and vials that were tested for complement activation.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13] Some of these ADRs are quite common. For example, hypersensitivity reactions after the first exposure to rituximab are reported in about half of patients with B-cell malignancies, 14 14.5% of patients were reported to experience severe infusion reactions in response to the first administration of cetuximab, 15 and 12.3% of patients receiving infusions of the anti-TNF-a antibody infliximab experienced infusion reactions. 16 Anaphylaxis, hypersensitivity, and increased (undesired) antibody responses all can result from complement activation.…”

Incidence and associated factors of cetuximab-induced hypersensitivity infusion reactions in 1392 cancer patients treated in four French areas: a possible association with Lyme disease?

“…In southeastern states of the United State of America (USA), an increased incidence of CI-IRs was observed in real life during post-marketing surveillance [ 21 – 23 , 26 , 28 , 30 – 33 ]. High rates of severe CI-IRs have been reported in North Carolina (14.4%), Tennessee (14%), Missouri (24.6%), Oklahoma (12.4%), Florida (27%) and Arkansas (14.5%) [ 21 , 23 , 26 , 28 , 30 , 33 ].…”

“…In southeastern states of the United State of America (USA), an increased incidence of CI-IRs was observed in real life during post-marketing surveillance [ 21 – 23 , 26 , 28 , 30 – 33 ]. High rates of severe CI-IRs have been reported in North Carolina (14.4%), Tennessee (14%), Missouri (24.6%), Oklahoma (12.4%), Florida (27%) and Arkansas (14.5%) [ 21 , 23 , 26 , 28 , 30 , 33 ]. Hypotheses have been put forward that a history of lone star tick (Amblyomma americanum) bites prior to cetuximab infusion could generate crossed reactions between cetuximab and alpha-gal, an oligosaccharide also observed in cetuximab heavy chain, through IgE [ 12 , 13 , 15 , 16 , 31 , 34 – 39 , 40 , 41 ].…”

Incidence and associated factors of cetuximab-induced hypersensitivity infusion reactions in 1392 cancer patients treated in four French areas: A possible association with Lyme disease?

“…Geography, allergy history, cancer type (HNSCC), ethnic group, premedication, tobacco and alcohol consumption have been reported as potential risk factors for CI-IRs, but these factors remain controversial [21][22][23][24][25][26][27][28][29].…”