(051) Correlation between COVID vaccinations and infusion-related hypersensitivity reactions with the administration of paclitaxel and docetaxel in patients being treated for gynecologic malignancies

Poster Abstract:

Background: Taxanes are FDA approved therapies commonly used to treat patients with gynecologic malignancies. Infusion-related hypersensitivity reactions to paclitaxel and docetaxel are often attributed to the excipients such as the Kolliphor El (MW 2500) and polysorbate-80 (MW 1300). Current manufacturer and CDC recommendations are to avoid use of the COVID vaccines if a person has a known hypersensitivity to any of the ingredients in the vaccine formulation, including the above PEG components. There have been recent case reports of not only allergic reactions to the COVID vaccines, but also increased risk of hypersensitivity reactions during taxane administration.

Objectives: Primary To determine if there is an increase in the rate and severity of infusion-related reactions when administering paclitaxel and docetaxel in the treatment of gynecologic malignancies in the outpatient setting following the introduction of COVID vaccination in 2021. Secondary To determine relative risk of developing infusion-related reaction among patients who received COVID vaccination prior to starting paclitaxel/docetaxel for the treatment of gynecologic malignancies vs those who did not receive the vaccination prior to starting paclitaxel/docetaxel.

Methods: This study will be an interrupted time series and retrospective cohort study of patients with gynecologic malignancies whose treatment included either paclitaxel or docetaxel between November 2018 and May 2023. Vaccination status for the COVID virus will be obtained for the patients treated from 2021 to 2023. Patient profiles will be reviewed to determine taxane administration and documented hypersensitivity reactions in correlation to vaccination status.

Results: Pending.
Conclusion/

Discussion: Pending.

References (must also be included in final poster):

References: To be added to poster (compacted list not included in abstract submission)
1. Pfizer-BioNTech COVID-19 Vaccine [package insert]. New York, NY: Pfizer, Inc. 2021
2. Moderna COVID-19 Vaccine [package insert]. Cambridge, MA: Moderna US, Inc. 2021
3. Janssen COVID-19 Vaccine [package insert]. Horsham, PA: Janssen Biotech, Inc. 2021
4. Weiss RB, Donehower RC, Wiernik PH, Ohnuma T, Gralla RJ, Trump DL, Baker JR Jr, Van Echo DA, Von Hoff DD, Leyland-Jones B. Hypersensitivity reactions from taxol. J Clin Oncol. 1990 Jul;8(7):1263-8. doi: 10.1200/JCO.1990.8.7.1263. PMID: 1972736.
5. Paclitaxel injection, USP [package insert]. Lake Forest, IL: Hospira, Inc. 2021
6. Szebeni J, Muggia FM, Alving CR. Complement activation by Cremophor EL as a possible contributor to hypersensitivity to paclitaxel: an in vitro study. J Natl Cancer Inst. 1998 Feb 18;90(4):300-6. doi: 10.1093/jnci/90.4.300. PMID: 9486816.
7. Schwartzberg LS, Navari RM. Safety of Polysorbate 80 in the Oncology Setting. Adv Ther. 2018;35(6):754-767. doi:10.1007/s12325-018-0707-z
8. Szebeni J. Complement activation-related pseudoallergy: a stress reaction in blood triggered by nanomedicines and biologicals. Mol Immunol. 2014 Oct;61(2):163-73. doi: 10.1016/j.molimm.2014.06.038. Epub 2014 Aug 12. PMID: 25124145.
9. Gelderblom H, Verweij J, Nooter K, Sparreboom A. Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation. Eur J Cancer. 2001 Sep;37(13):1590-8. doi: 10.1016/s0959-8049(01)00171-x. PMID: 11527683.
10. Shegokar R, Athawale R, Kurup N, Yang R, Chougule M, (2017) Nanotechnology-Based Approaches for Targeting and Delivery of Drugs and Genes. https://doi.org/10.1016/B978-0-12-809717-5.00011-7. https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/cremophor.
11. Kolliphor®EL, Polyoxyl 35 Castor Oil USP-NF [technical information]. Ludwigshafen, Germany: BASF SE. 2019 https://pharmaceutical.basf.com/global/en/drug-formulation/products/kolliphor-el.html
12. Kolliphor®EL, Polyoxyl 35 Castor Oil USP-NF [technical information]. Ludwigshafen, Germany: BASF SE. 2019 file:///C:/Users/shayward/AppData/Local/Temp/kolliphor-el_technical_information.pdf
13. Surapaneni MS, Das SK, Das NG. Designing Paclitaxel drug delivery systems aimed at improved patient outcomes: current status and challenges. ISRN Pharmacol. 2012;2012:623139. doi:10.5402/2012/623139
14. Weiszhár Z, Czúcz J, Révész C, Rosivall L, Szebeni J, Rozsnyay Z. Complement activation by polyethoxylated pharmaceutical surfactants: Cremophor-EL, Tween-80 and Tween-20. Eur J Pharm Sci. 2012 Mar 12;45(4):492-8. doi: 10.1016/j.ejps.2011.09.016. Epub 2011 Sep 22. PMID: 21963457.
15. Polysorbate-80, Excipient, pharmacologically inactive substance (2021, May 10th) Retrieved from https://www.drugs.com/inactive/polysorbate-80-372.html
16. Sellaturay P, Nasser S, Islam S, Gurugama P, Ewan P. Polyethelyne Glycol (PEG) is a cause of anaphylaxis to thePfizer/BioNTech mRNA COVID-19 vaccine. Clinical & Experimental Allergy. 2021 Apr; 51(6):861-3. doi/10.1111/cea.13874
17. Stone CA Jr, Liu Y, Relling MV, et al. Immediate Hypersensitivity to Polyethylene Glycols and Polysorbates: More Common Than We Have Recognized. J Allergy Clin Immunol Pract. 2019;7(5):1533-1540.e8. doi:10.1016/j.jaip.2018.12.003
18. Kolliphor®EL, Polyoxyl 35 Castor Oil [technical information]. Darmstadt, Germany: Millipore Sigma/Merck KGaA 2021. https://www.sigmaaldrich.com/US/en/product/sigma/c5135?gclid=Cj0KCQjw1dGJBhD4ARIsANb6OdnlNzungvZ93A9du6rSLUv72jU2e03I28AQUPNLbTcn2hfwKnAAJLUaAkAIEALw_wcB#
19. Polysorbate-80 USP [technical information]. Darmstadt, Germany: Millipore Sigma/Merck KGaA 2021. https://www.sigmaaldrich.com/US/en/product/usp/1547969?context=product
20. PEG Linkers, PEG in Nanopartical Drug Delivery (2021) BroadPharm®. Retreived from https://broadpharm.com/web/products.php?category1=peg-linkers
21. Polyethylene Glycol, Excipient, pharmacologically inactive substance (2021, April 12) Retrieved from https://www.drugs.com/inactive/polyethylene-glycol-177.html
22. Excipients in Vaccines per 0.5ml Dose (2021, Jan 15) Institute for Vaccine Safety Johns Hopkins Bloomberg School of Public Health. Retrieved from https://www.vaccinesafety.edu/components-Excipients.htm
23. Wenande E, Garvey LH. Immediate-type hypersensitivity to polyethylene glycols: a review. Clinical & Experimental Allergy. 2016 May; 46(7): 907-922 doi/10.1111/cea.12760
24. Robinson R, Cross-reactivity between propylene glycol and macrogol? Ask the Expert American Academy of Allergy Asthma and Immunology (2019, July 7) Retrieved from https://www.aaaai.org/allergist-resources/ask-the-expert/answers/old-ask-the-experts/cross-reactivity-between-propylene-glycol-and-macrgols
25. Shavit R, Maoz-Segal R, Iancovici-Kidon M, et al. Prevalence of Allergic Reactions After Pfizer-BioNTech COVID-19 Vaccination Among Adults With High Allergy Risk. JAMA Netw Open. 2021;4(8):e2122255. doi:10.1001/jamanetworkopen.2021.22255
26. Osantowski et.al. Hypersensitivity reaction to taxanes following COVID-19 vaccination. Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 3092-3092.