Guideline sources The following summarized guidelines for the evaluation and management of hypersensitivity reactions to chemotherapy are prepared by our editorial team based on guidelines from the European Academy of Allergy and Clinical Immunology (EAACI 2022), the European Society of Medical Oncology (ESMO 2017), and the Comit de l' volution de la pratique en oncologie (CEPO 2014). 1 2 3 Guidelines 1. Screening and diagnosis Pathogenesis: Recognize the pathogenetic mechanisms of hypersensitivity reactions to different chemotherapeutic agents: Situation Guidance IgE-mediated reactions in some immediate, often severe cases B Platinum compounds https://web.pathway.md/diseases/recXCuhDZ7scNuvWY 1/5 6/24/23, 12:45 PM Hypersensitivity reactions to chemotherapy Pathway Direct activation of complement system by the drug in the majority of cases Taxanes IgE-mediated reactions in some cases B Immunologic and non-immunologic mechanisms. B Epipodophyllotoxins 2. Classification and risk stratification Risk factors: take into account other risk factors apart from being aware of the potential risk of an infusion reaction of a specific drug, when delivering anticancer drugs, and during which course it is most likely to happen. B Show 2 more Severity grading: as per ESMO 2017 guidelines, grade adverse reactions in a standardized way to evaluate the severity of an infusion reaction. B 3. Diagnostic investigations Skin testing: As per EAACI 2022 guidelines, recognize that skin testing is the most readily available diagnostic test. B Show 3 more As per CEPO 2014 guidelines, consider obtaining skin testing (prick and intradermal) in patients with suspected hypersensitivity to platinum drugs, whenever possible. Obtain the test at least 2- 6 weeks after a hypersensitivity reaction. C Show 2 more Drug provocation test: Obtain drug provocation testing as the gold standard for the diagnosis of hypersensitivity reactions to drugs A , and to help avoid a significant number of patients from unnecessary drug desensitizations. B Recognize that drug provocation testing is a high-risk technique and benefits from dedicated spaces and expert personnel, while has a good safety profile when performed in specialist centers. B In vitro IgE testing: consider obtaining in vitro detection of specific IgE for platinum compounds for the diagnosis of hypersensitivity reactions to these drugs. C Tryptase and histamine tests: do not obtain serum tryptase, serum and urine histamine tests in patients with anaphylaxis, as these tests are not universally available, not carried out on an emergency basis and not specific for anaphylaxis. D https://web.pathway.md/diseases/recXCuhDZ7scNuvWY 2/5 6/24/23, 12:45 PM Hypersensitivity reactions to chemotherapy Pathway 4. Medical management Observation: Recognize that prompt recognition and immediate medical attention are essential. Recognize that some patients feel odd or uncomfortable or express a need to urinate or defecate before an infusion reaction. Pay serious attention to those symptoms and evaluate the patient by measuring BP and pulse rate. B Initial supportive therapy: discontinue the administration of medication caused infusion reaction. B Show 10 more Management of anaphylaxis: administer epinephrine immediately at a dose of 0.01 mg/kg, 1 mg/mL dilution to a maximum total dose of 0.5 mL, intramuscularly into the lateral thigh muscle in patients fulfilling any of the three criteria of anaphylaxis. B Consider repeated administration every 5-15 minutes. B Administer IV epinephrine after a failure of a prompt response with severe hypotension or cardiac arrest. B Show 6 more Drug desensitization: As per EAACI 2022 guidelines, perform rapid drug desensitization in patients with immediate reactions, anaphylaxis and delayed reactions non-severe cutaneous adverse reactions. B Show 2 more As per ESMO 2017 guidelines, consider performing desensitization in patients with grade 3/4 infusion reaction caused by carboplatin, oxaliplatin, docetaxel, anthracyclines, or etoposide. C As per CEPO 2014 guidelines, consider using a multi-step desensitization protocol in case of a positive skin test for platinum drugs or a type I hypersensitivity reaction, if treatment cannot be substituted and if stopping treatment would affect the patient's survival. C Show 6 more 5. Nonpharmacologic interventions Psychological support: Provide psychological intervention to alleviate symptoms of uncertainty related to a potential infusion reaction with anticancer drugs. B Provide psychological support and have a complete, informative discussion with the patient about the potential benefits of continuing with the drug and the risk of infusion reaction recurrence. B 6. Preventative measures Preparation before drug delivery: elicit a medical history, ask about previous allergic disorders, atopic status and concomitant treatments before the administration of any drug. B https://web.pathway.md/diseases/recXCuhDZ7scNuvWY 3/5 6/24/23, 12:45 PM Hypersensitivity reactions to chemotherapy Pathway Show 2 more Premedication: As per EAACI 2022 guidelines, administer premedication with corticosteroids and antihistamines (such as dexametasone 20 mg and chlorpheniramine 10 mg IV 1 hour before chemotherapy) for the prevention of moderate-to-severe infusion reactions to taxanes. B Show 2 more As per ESMO 2017 guidelines, administer premedication with corticosteroids and antihistamines in patients before taxane B , asparaginase and etoposide infusion. B Show 6 more As per CEPO 2014 guidelines: Do not administer routine premedication with corticosteroids and antihistamines before platinum agents infusion. D Administer routine premedication with corticosteroids and H1RAs and H1RAs before taxanes infusion. A Rate of administration: as per ESMO 2017 guidelines, slow the infusion rate of anthracyclines. B Show 5 more Prevention of future episodes: attempt to establish, based on the precipitating drug and the characteristics of the event, the steps that could be taken to prevent future episodes following any infusion reaction episode. B 7. Follow-up and surveillance Post-reaction monitoring: obtain close observation for 24 hours after a severe reaction. Monitor vital signs and control recurrence symptoms. B Show 3 more Rechallenge: decide on restoring treatment based on the severity and nature of the reaction as well as clinical factors such as the risk of a serious recurrent reaction and the potential clinical benefit of further treatment. B Show 2 more 8. Quality improvement Reporting: ensure accurate documentation of the infusion reaction episode, including pre-infusion assessments, an appropriate description and grading of the infusion reaction (according to accepted classifications such as CTCAE), and how it was managed. B References https://web.pathway.md/diseases/recXCuhDZ7scNuvWY 4/5 6/24/23, 12:45 PM Hypersensitivity reactions to chemotherapy Pathway 1. S Rosell , I Blasco, L Garc a Fabregat et al. Management of infusion reactions to systemic anticancer therapy: ESMO Clinical Practice Guidelines. Ann Oncol. 2017 Jul 1;28(suppl_4):iv100-iv118. Open 2. J Boulanger, J N Boursiquot, G Cournoyer et al. Management of hypersensitivity to platinum- and taxane-based chemotherapy: cepo review and clinical recommendations. Curr Oncol. 2014 Aug;21 4):e630 41. Open 3. Mauro Pagani, Sevim Bavbek, Emilio Alvarez-Cuesta et al. Hypersensitivity reactions to chemotherapy: an EAACI Position Paper. Allergy. 2022 Feb;77 2 388 403. Open 4. David A Khan, Aleena Banerji, Kimberly G Blumenthal et al. Drug Allergy: A 2022 Practice Parameter Update. J Allergy Clin Immunol. 2022 Sep 16;S0091 6749 22 01186 1. Open https://web.pathway.md/diseases/recXCuhDZ7scNuvWY 5/5