Prevalence and management of immediate drug hypersensitivity observed during antineoplastic drug therapy

Authors

DOI:

https://doi.org/10.2340/1651-226X.2025.43098

Keywords:

allergic reaction, Cancer chemotherapy, monoclonal antibodies, checkpoint inhibitor, pretreatment, Rechallenge

Abstract

Background: Immediate drug hypersensitivity reactions (IDHRs) complicate the treatment of patients with cancer. Rapid drug desensitization (RDD) is not a standard treatment option in Northern Europe as in Southern Europe and the US. Thus, in Denmark, allergists are not involved when cancer treatments are complicated by IDHRs.

Purpose: The purpose was to investigate whether Danish patients could benefit from the implementation of an allergy work-up including RDD by investigating the magnitude of the problem with IDHRs in Danish antineoplastic drug therapy, in addition to describe characteristics of IDHRs, re-treatment strategies, and outcomes.

Patients and methods: This prospective observational single-center study was conducted at a large university hospital. Patients were included over 17 months. Patients were interviewed during index reaction. Information on culprit drug, infusion procedure, and premedication was obtained, together with reaction phenotype and severity. After 3 months, information on re-treatment strategies and outcome were obtained from medical records.

Results: In total, 126 patients experienced IDHRs during the study period. This corresponds to 2.5% of patients receiving antineoplastic drug therapy. Re-treatment, using increased premedication and/or decreased infusion rate, was attempted in 97 patients and tolerated by 69. However, 57 out of 126 patients (45%) discontinued treatment. This corresponds to 1.1% of patients receiving antineoplastic drug therapy.

Patients with gynecologic cancers had a particularly high risk.

Interpretation: IDHRs are infrequent in antineoplastic drug therapy, but due to the large number of patients with cancer, the number of IDHRs is significant. Patients discontinuing treatment could benefit from an allergy work-up including RDD.

Downloads

Download data is not yet available.

References

Alvarez-Cuesta E, Madrigal-Burgaleta R, Broyles AD, Cuesta-Herranz J, Guzman-Melendez MA, Maciag MC, et al. Standards for practical intravenous rapid drug desensitization & delabeling: a WAO committee statement. World Allergy Organ J. 2022;15(6):100640.

https://doi.org/10.1016/j.waojou.2022.100640 DOI: https://doi.org/10.1016/j.waojou.2022.100640

Pagani M, Bavbek S, Alvarez-Cuesta E, Berna Dursun A, Bonadonna P, Castells M, et al. Hypersensitivity reactions to chemotherapy: an EAACI Position Paper. Allergy. 2021;77(2):388–403. DOI: https://doi.org/10.1111/all.15113

https://doi.org/10.22541/au.161726282.21370610/v1 DOI: https://doi.org/10.22541/au.161726282.21370610/v1

Pagani M. The complex clinical picture of presumably allergic side effects to cytostatic drugs: symptoms, pathomechanism, reexposure, and desensitization. Med Clin North Am. 2010;94(4):835–52, xiii.

https://doi.org/10.1016/j.mcna.2010.03.002 DOI: https://doi.org/10.1016/j.mcna.2010.03.002

Picard M, Castells MC. Re-visiting hypersensitivity reactions to taxanes: a comprehensive review. Clin Rev Allergy Immunol. 2015;49(2):177–91.

https://doi.org/10.1007/s12016-014-8416-0 DOI: https://doi.org/10.1007/s12016-014-8416-0

Navo M, Kunthur A, Badell ML, Coffer LW, 2nd, Markman M, Brown J, et al. Evaluation of the incidence of carboplatin hypersensitivity reactions in cancer patients. Gynecol Oncol. 2006;103(2):608–13.

https://doi.org/10.1016/j.ygyno.2006.04.002 DOI: https://doi.org/10.1016/j.ygyno.2006.04.002

Rogers BB, Cuddahy T, Briscella C, Ross N, Olszanski AJ, Denlinger CS. Oxaliplatin: Detection and management of hypersensitivity reactions. Clin J Oncol Nurs. 2019;23(1):68–75.

https://doi.org/10.1188/19.CJON.68-75 DOI: https://doi.org/10.1188/19.CJON.68-75

Bavbek S, Pagani M, Alvarez-Cuesta E, Castells M, Dursun AB, Hamadi S, et al. Hypersensitivity reactions to biologicals: an EAACI position paper. Allergy. 2021;77(1):39–54. DOI: https://doi.org/10.1111/all.14984

https://doi.org/10.22541/au.161718382.20133527/v1 DOI: https://doi.org/10.22541/au.161718382.20133527/v1

Hiraizumi K, Honda C, Watanabe A, Nakao T, Midorikawa S, Abe H, et al. Safety of nivolumab monotherapy in five cancer types: pooled analysis of post-marketing surveillance in Japan. Int J Clin Oncol. 2024;29(7):932–43.

https://doi.org/10.1007/s10147-024-02515-1 DOI: https://doi.org/10.1007/s10147-024-02515-1

Yamamoto N, Nakanishi Y, Gemma A, Nakagawa K, Sakamoto T, Akamatsu A, et al. Real-world safety of nivolumab in patients with non-small-cell lung cancer in Japan: postmarketing surveillance. Cancer Sci. 2021;112(11):4692–701.

https://doi.org/10.1111/cas.15117 DOI: https://doi.org/10.1111/cas.15117

Momtaz P, Park V, Panageas KS, Postow MA, Callahan M, Wolchok JD, et al. Safety of infusing ipilimumab over 30 minutes. J Clin Oncol. 2015;33(30):3454–8.

https://doi.org/10.1200/JCO.2015.61.0030 DOI: https://doi.org/10.1200/JCO.2015.61.0030

Jakubovic BD, Vecillas LL, Jimenez-Rodriguez TW, Sanchez-Sanchez S, Castells M. Drug hypersensitivity in the fast lane: what clinicians should know about phenotypes, endotypes, and biomarkers. Ann Allergy Asthma Immunol. 2020;124(6):566–72.

https://doi.org/10.1016/j.anai.2020.04.005 DOI: https://doi.org/10.1016/j.anai.2020.04.005

Isabwe GAC, Garcia Neuer M, De Las Vecillas Sanchez L, Lynch DM, Marquis K, Castells M. Hypersensitivity reactions to therapeutic monoclonal antibodies: phenotypes and endotypes. J Allergy Clin Immunol. 2018;142(1):159–70.e2.

https://doi.org/10.1016/j.jaci.2018.02.018 DOI: https://doi.org/10.1016/j.jaci.2018.02.018

Silver J, Garcia-Neuer M, Lynch DM, Pasaoglu G, Sloane DE, Castells M. Endophenotyping oxaliplatin hypersensitivity: personalizing desensitization to the atypical platin. J Allergy Clin Immunol Pract. 2020;8(5):1668–80.e2.

https://doi.org/10.1016/j.jaip.2020.02.013 DOI: https://doi.org/10.1016/j.jaip.2020.02.013

O’Cearbhaill R, Zhou Q, Iasonos A, Hensley ML, Tew WP, Aghajanian C, et al. The prophylactic conversion to an extended infusion schedule and use of premedication to prevent hypersensitivity reactions in ovarian cancer patients during carboplatin retreatment. Gynecol Oncol. 2010;116(3):326–31.

https://doi.org/10.1016/j.ygyno.2009.10.070 DOI: https://doi.org/10.1016/j.ygyno.2009.10.070

Lenz HJ. Management and preparedness for infusion and hypersensitivity reactions. Oncologist. 2007;12(5):601–9.

https://doi.org/10.1634/theoncologist.12-5-601 DOI: https://doi.org/10.1634/theoncologist.12-5-601

Markman M, Kennedy A, Webster K, Kulp B, Peterson G, Belinson J. Paclitaxel-associated hypersensitivity reactions: experience of the gynecologic oncology program of the Cleveland Clinic Cancer Center. J Clin Oncol. 2000;18(1):102–5.

https://doi.org/10.1200/JCO.2000.18.1.102 DOI: https://doi.org/10.1200/JCO.2000.18.1.102

Banerji A, Lax T, Guyer A, Hurwitz S, Camargo CA, Jr., Long AA. Management of hypersensitivity reactions to Carboplatin and Paclitaxel in an outpatient oncology infusion center: a 5-year review. J Allergy Clin Immunol Pract. 2014;2(4):428–33.

https://doi.org/10.1016/j.jaip.2014.04.010 DOI: https://doi.org/10.1016/j.jaip.2014.04.010

Broyles AD, Banerji A, Barmettler S, Biggs CM, Blumenthal K, Brennan PJ, et al. Practical guidance for the evaluation and management of drug hypersensitivity: specific drugs. J Allergy Clin Immunol Pract. 2020;8(9s):S16–S116.

https://doi.org/10.1016/j.jaip.2020.08.002 DOI: https://doi.org/10.1016/j.jaip.2020.08.002

Park BC, Stone CA Jr., Dewan AK, Johnson DB. Hypersensitivity reactions and immune-related adverse events to immune checkpoint inhibitors: approaches, mechanisms, and models. Immunol Allergy Clin North Am. 2022;42(2):285–305.

https://doi.org/10.1016/j.iac.2021.12.006 DOI: https://doi.org/10.1016/j.iac.2021.12.006

Markman M, Kennedy A, Webster K, Elson P, Peterson G, Kulp B, et al. Clinical features of hypersensitivity reactions to carboplatin. J Clin Oncol. 1999;17(4):1141.

https://doi.org/10.1200/JCO.1999.17.4.1141 DOI: https://doi.org/10.1200/JCO.1999.17.4.1141

Tsao LR, Young FD, Otani IM, Castells MC. Hypersensitivity reactions to platinum agents and taxanes. Clin Rev Allergy Immunol. 2022;62(3):432–48.

https://doi.org/10.1007/s12016-021-08877-y DOI: https://doi.org/10.1007/s12016-021-08877-y

Madrigal-Burgaleta R, Bernal-Rubio L, Berges-Gimeno MP, Carpio-Escalona LV, Gehlhaar P, Alvarez-Cuesta E. A large single-hospital experience using drug provocation testing and rapid drug desensitization in hypersensitivity to antineoplastic and biological agents. J Allergy Clin Immunol Pract. 2019;7(2):618–32.

https://doi.org/10.1016/j.jaip.2018.07.031 DOI: https://doi.org/10.1016/j.jaip.2018.07.031

Danish Health Authorities. Specialty guideline for clinical oncology 2023. [Citation date: 10.01.2025] Available from: https://www.sst.dk/-/media/Viden/Specialplaner/Specialeplan-for-klinisk-onkologi/Specialevejledning-for-Klinisk-onkologi-den-25-juli-2023.ashx?sc_lang=da&hash=6DCD53183F1ABB1B488D9053EA6B6CFF

Danish Health Authorities. Specialty guideline for clinical hematology 2023. [Citation date: 10.01.2025] Available from: https://www.sst.dk/-/media/Viden/Specialplaner/Specialeplan-for-intern-medicin-haematologi/Specialevejledning-for-Intern-medicin-Haematologi-den-15-marts-2023.ashx

Cheung EM, Edenfield WJ, Mattar B, Anthony SP, Mutch PJ, Chanas B, et al. Safety and pharmacokinetics of bendamustine rapid-infusion formulation. J Clin Pharmacol. 2017;57(11):1400–8.

https://doi.org/10.1002/jcph.942 DOI: https://doi.org/10.1002/jcph.942

Santos RB, Galvão VR. Monoclonal antibodies hypersensitivity: prevalence and management. Immunol Allergy Clin North Am. 2017;37(4):695–711.

https://doi.org/10.1016/j.iac.2017.07.003 DOI: https://doi.org/10.1016/j.iac.2017.07.003

Zwimpfer TA, Bilir E, Gasimli K, Cokan A, Bizzarri N, Razumova Z, et al. Management of patients with hypersensitivity to platinum salts and taxane in gynecological cancers: a cross-sectional study by the European Network of Young Gynaecologic Oncologists (ENYGO). Cancers (Basel). 2024;16(6):1155.

https://doi.org/10.3390/cancers16061155 DOI: https://doi.org/10.3390/cancers16061155

Chung CH. Managing premedications and the risk for reactions to infusional monoclonal antibody therapy. Oncologist. 2008;13(6):725–32.

https://doi.org/10.1634/theoncologist.2008-0012 DOI: https://doi.org/10.1634/theoncologist.2008-0012

Cardona V, Ansotegui IJ, Ebisawa M, El-Gamal Y, Fernandez Rivas M, Fineman S, et al. World allergy organization anaphylaxis guidance 2020. World Allergy Organ J. 2020;13(10):100472.

https://doi.org/10.1016/j.waojou.2020.100472 DOI: https://doi.org/10.1016/j.waojou.2020.100472

Published

2025-04-28

How to Cite

Rasmussen, T. H., Mortz, C. G., Pfeiffer, P., Andersen, N., & Bindslev-Jensen, C. (2025). Prevalence and management of immediate drug hypersensitivity observed during antineoplastic drug therapy. Acta Oncologica, 64, 574–584. https://doi.org/10.2340/1651-226X.2025.43098

Issue

Section

Original article