Patients tolerate COVID-19 mRNA vaccines despite taxane hypersensitivity

According to a study published in The Journal of Allergy and Clinical Immunology: In Practice.

This research is the largest evaluation of the safety of these vaccines in patients who have previously had reactions to chemotherapies including polyethylene glycol derivatives (PEG), Leila A. AlenazyMD, MMSc, an allergy and clinical immunology fellow in the division of allergy and clinical immunology in the department of medicine at the McGill University Health Center in Montreal, and his colleagues wrote.

According to the researchers, the chemotherapy drug paclitaxel is a commonly used taxane that includes Cremophor EL, a low molecular weight PEG. Cremophor EL is also present in the messenger RNA (mRNA) COVID-19 vaccines BNT162b2 Pfizer-BioNTech and mRNA-1273 Moderna. However, the researchers noted that the role of PEG in anaphylaxis caused by COVID-19 mRNA vaccines remains unknown.

Also, docetaxel, another taxane, includes polysorbate 80, which is an excipient used in the AstraZeneca and Janssen COVID-19 vaccines.

Between January 1 and October 31, 2021, researchers evaluated 26 patients (mean age, 61 years; 100% female; 84.6% Caucasian) who had a history of cremophore-related paclitaxel reactions (n= 23), docetaxel (n = 2) or both (n = 1).

Each patient was skin tested for high and low molecular weight PEG and polysorbate 80. Additionally, patients were challenged with PEG 3,350 or had a direct challenge with Pfizer-BioNTech vaccines, Moderna or AstraZeneca COVID-19. 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 pruritus in 3.8%, followed by dyspnea in 42.3%, back pain in 38 .5% and chest heaviness in 15.4%.

Initial reactions included non-IgE-mediated type I reactions in 50% of patients, cytokine release reactions in 23%, immediate mixed reactions in 23%, and delayed type IV reactions in 3.8%. The severity of initial hypersensitivity reactions included mild reactions in seven patients, moderate reactions in 18, and severe reaction in one.

All of these hypersensitivity reactions occurred within 60 minutes of infusion, except in one patient. Additionally, none of these patients had a previous anaphylactic reaction to taxanes, and none required epinephrine.

Following hypersensitivity reactions, most patients subsequently tolerated paclitaxel and/or docetaxel with an H1 and H2 receptor antagonist antihistamine and/or corticosteroid premedication (n=25) and slower infusions (n=22 ). One of the patients was desensitized to paclitaxel, two switched to another drug and one stopped paclitaxel.

In addition, 19 patients had PEG and PEG-derivative negative TPS. Three patients underwent graded provocations with PEG 3350 and had negative results.

Upon completion of testing, all patients successfully received a COVID-19 mRNA vaccine without any evidence of immediate or delayed hypersensitivity reactions and without any premedication.

All but one patient who tolerated the mRNA vaccines had a mild to moderate taxane hypersensitivity reaction. The remaining patient had a severe hypersensitivity reaction, pneumonitis, after receiving paclitaxel. In addition, this patient tolerated the Moderna vaccine.

Another patient who reacted to PEG-doxorubicin and paclitaxel had a negative SPT in addition to a negative PEG 3350 oral challenge and tolerated the Pfizer-BioNTech vaccine.

Noting that all patients had a negative SPT for the higher and lower molecular weight PEG derivatives, the researchers found that they would be less likely to react to the PEG derivatives used in the study.

Patients who did not have PTS tolerated COVID-19 vaccines, the researchers continued, leading the researchers to conclude that skin tests are not necessary to assess the safety of COVID-19 vaccines after reactions to hypersensitivity to taxanes.

In other words, the researchers wrote, patients who had previous hypersensitivity reactions to paclitaxel with the Cremophor EL vehicle or to docetaxel with the polysorbate 80 vehicle tolerated the COVID-19 vaccines safely. Patients with a similar history of taxane hypersensitivity reactions could then be safely given these vaccines, the researchers added, without prior PTS or premedication.