Patients tolerate mRNA COVID-19 vaccines despite hypersensitivity to taxanes
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Patients with a history of mild to moderate hypersensitivity reactions to taxanes safely received the mRNA vaccines for COVID-19, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.
This research is the largest safety evaluation of these vaccines in patients who have had prior reactions to chemotherapies that include polyethylene glycol (PEG) derivatives, Leila A. Alenazy, MD, MMSc, an allergy and clinical immunology fellow with the division of allergy and clinical immunology in the department of medicine at McGill University Health Centre in Montreal, and colleagues wrote.
According to the researchers, the chemotherapeutic agent paclitaxel is a commonly used taxane that includes Cremophor EL, a PEG with small molecular weight. Cremophor EL also is in the BNT162b2 Pfizer-BioNTech and mRNA-1273 Moderna messenger RNA (mRNA)-based COVID-19 vaccines. However, the researchers noted that the role of PEG in anaphylaxis caused by mRNA COVID-19 vaccines remains unknown.
Also, docetaxel, another taxane, includes polysorbate 80, which is an excipient that is used in AstraZeneca and Janssen COVID-19 vaccines.
Between Jan. 1 and Oct. 31, 2021, the researchers assessed 26 patients (mean age, 61 years; 100% female; 84.6% white) who had a history of reactions to cremophor-bound paclitaxel (n = 23), docetaxel (n = 2) or both (n = 1).
Each patient had a skin prick test for PEG with high and low molecular weight and for polysorbate 80. Also, patients were challenged with PEG 3,350 or had a direct challenge with the Pfizer-BioNTech, Moderna or AstraZeneca COVID-19 vaccines. The researchers then contacted the patients a week later to assess delayed reactions.
Initial symptoms were cutaneous and included flushing in 65% of patients, urticaria in 7.6% and pruritis in 3.8%, followed by dyspnea in 42.3%, back pain in 38.5% and chest heaviness in 15.4%.
Initial reactions included type I non-IgE mediated reactions in 50% of patients, cytokine-release reactions in 23%, mixed immediate reactions in 23% and delayed-type IV reactions in 3.8%. Severity of initial hypersensitivity reactions included mild reactions in seven patients, moderate reactions in 18 and a severe reaction in one.
All of these hypersensitivity reactions occurred within 60 minutes of infusion except for one patient. Also, none of these patients had any prior anaphylactic reactions to taxanes, nor did anyone require epinephrine.
After the hypersensitivity reactions, most of the patients then tolerated paclitaxel and/or docetaxel with antihistamine H1 and H2 receptor antagonist and/or corticosteroid premedication (n = 25) and slower infusions (n = 22). One of the patients was desensitized to paclitaxel, two switched to an alternative drug and one discontinued paclitaxel.
Also, 19 patients had negative SPTs to PEG and PEG derivatives. Three patients had PEG 3,350 graded challenges and had negative results.
Once testing was complete, all of the patients received an mRNA COVID-19 vaccine successfully without any evidence of immediate or delayed hypersensitivity reactions and without any premedication.
All but one of the patients who tolerated the mRNA vaccines had a previous mild to moderate taxane hypersensitivity reaction. The remaining patient had a severe hypersensitivity reaction, pneumonitis, after receiving paclitaxel. Also, this patient tolerated the Moderna vaccine.
Another patient who had reacted to PEG-doxorubicin and paclitaxel had a negative SPT in addition to a negative oral challenge to PEG 3,350 and tolerated the Pfizer-BioNTech vaccine.
Noting that all the patients had negative SPT for PEG derivatives of higher and lower molecular weights, the researchers found that they would be less likely to react to the PEG derivatives that were used in the study.
The patients who did not have SPT tolerated the COVID-19 vaccines, the researchers continued, leading the researchers to conclude that skin testing is not necessary for evaluating the safety of COVID-19 vaccines after hypersensitivity reactions to taxanes.
In other words, the researchers wrote, patients who had previous hypersensitivity reactions to paclitaxel with the excipient Cremophor EL or docetaxel with the excipient polysorbate 80 tolerated COVID-19 vaccines safely. Patients with similar histories of taxane hypersensitivity reactions could then receive these vaccines safely too, the researchers added, without prior SPT or premedication.
Perspective
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With our experience, research and data from our own group, these findings are not surprising but instead reassuring and confirm our experience.
First, we have learned based on additional research this year that PEG and polysorbate excipients are not likely the cause of mRNA vaccine reactions. Second, we published a similar article showing that COVID-19 vaccines were tolerated in individuals not only with paclitaxel allergy but also with docetaxel allergy.
Also, these findings are very consistent with our own recommendations for patients with allergic reactions to paclitaxel. They should proceed with mRNA COVID-19 vaccination, and excipient skin testing is not warranted prior to vaccination.
This paper adds further to the literature and provides reassurance on the tolerance of mRNA vaccines despite a paclitaxel allergy. However, we still need to better understand the cause of reactions in patients who have developed anaphylaxis. Research efforts there are ongoing, but there have been no clear answers yet.
References:
Wolfson AR, et al. J Allergy Clin Immunol Pract. 2021;doi:10.1016/j.jaip.2021.06.010.
Banerji A, et al. Allergy. 2022;doi:10.1111/all.15178.
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