Medical algorithm: Diagnosis and treatment of hypersensitivity reactions to cancer chemotherapy

Madrigal-Burgaleta, Ricardo; Vazquez-Revuelta, P.; Martí-Garrido, Jaume; Lleonart-Bellfill, Ramon; Ali, FR; Álvarez-Cuesta, Emilio

doi:10.1111/all.14810

Cited by 12 publications

(27 citation statements)

References 16 publications

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“…Comparison of diagnostic indexes as assessed in the largest reported series of platin-specific IgE appropriate facilities and specific resources; (ii) locally designed risk management strategies open to tailored plans based on individual assessment, phenotyping and endotyping; and (iii) access to expert personnel capable of appropriate patient selection and management provided the two previous pillars are met.Specifically, a recent article featured a practical diagnostic and therapeutic algorithm based on the current knowledge on the topic 90. …”

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confidence: 99%

Hypersensitivity reactions to chemotherapy: an EAACI Position Paper

Pagani

Bavbek

Álvarez-Cuesta

et al. 2021

Allergy

Self Cite

118

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Chemotherapeutic drugs have been widely used in the treatment of cancer disease for about 70 years. The development of new treatments has not hindered their use, and oncologists still prescribe them routinely, alone or in combination with other antineoplastic agents. However, all chemotherapeutic agents can induce hypersensitivity reactions (HSRs), with different incidences depending on the culprit drug. These reactions are the third leading cause of fatal drug-induced anaphylaxis in the United States. In Europe, deaths related to chemotherapy have also been reported. In particular, most reactions are caused by platinum compounds, taxanes, epipodophyllotoxins and asparaginase. Despite their prevalence and relevance, the ideal pathways for diagnosis, treatment and prevention of these reactions are still unclear, and practice remains considerably heterogeneous with vast differences from center to center. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology organized a task force to provide data and recommendations regarding the allergological work-up in this field of drug hypersensitivity reactions. This position paper aims to provide consensus on | 389 PAGANI et Al. 1 | INTRODUC TI ON Chemotherapeutic drugs have been used in the treatment of neoplasms since the 1940s. 1,2 Many types of antineoplastic agents were introduced in clinical practice and, despite the great diffusion of biological agents, chemotherapy (CHT) still represents the gold standard for the treatment of the majority of cancers, alone or in combination with the so-called more selective targeted therapies, namely monoclonal antibodies or other biologicals. 3 However, CHT can induce hypersensitivity reactions (HSRs) and remains the third leading cause of fatal drug-induced anaphylaxis in the United States. 4 Deaths related to CHT have also been reported in Europe. 5 This position paper aims to provide consensus on investigating HSRs to chemotherapeutic drugs and give practical recommendations for clinicians that treat these patients, such as oncologists, allergologists and internists. Key sections in this paper cover risk factors, pathogenesis, symptoms and signs of reactions, the role of skin tests, in vitro tests, indications and contraindications of drug provocations tests and desensitization of neoplastic patients with allergic reactions to CHT. Table 1 reports the main classes of CHT, their clinical indications, the characteristics of HSRs and their possible pathogenetic mechanisms. 2 | ME THODS This Position Paper was commissioned by the European Academy of Allergy and Clinical Immunology (EAACI). The task force group performed an intensive electronic literature search in MEDLINE, PubMed, databases of scientific societies, and reports of the AEMPS, European Medicines Agency, and the United States Food and Drug Administration by using the primary key words: hypersensitivity to chemotherapeutic drugs, hypersensitivity to antineoplastic agents, platinum compound hype...

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confidence: 99%

Hypersensitivity reactions to chemotherapy: an EAACI Position Paper

Pagani

Bavbek

Álvarez-Cuesta

et al. 2021

Allergy

Self Cite

118

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“…It rules out events other than HSRs thereby preventing unnecessary desensitization procedures. 8 , 10 , 24 , 25 However, we could not perform DPT as a part of the diagnostic approach, which is also a limitation of our study. The lack of local facilities for the implementation of DPT in our clinic prevented us from performing DPT.…”

Section: Discussionmentioning

confidence: 97%

Rapid drug desensitization with platin-based chemotherapy: Analysis of risk factors for breakthrough reactions

Akin

Erkoç

Öztürk

et al. 2022

World Allergy Organization Journal

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Background All platin-based chemotherapeutics can cause hypersensitivity reactions (HSRs). With rapid drug desensitization (RDD), few patients experience breakthrough reactions (BTR) during desensitization. However, data about risk factors for BTRs during RDD in patients with HSRs to platins are limited. We first aimed to describe characteristics of our platin-reactive population and to validate the Brigham and Women's Hospital's (BWH's) RDD protocol in our population along with their outcomes with RDD. Our second aim was to identify the risk factors for BTRs. Method This was a retrospective chart review (2013–2020) of patients with symptoms of immediate HSRs to platins. Initial HSRs were classified as grade 1, 2, or 3 based on their severity. Skin prick tests (SPT)/intradermal tests (IDT) were performed with implicated platins. A 12-step protocol was used during RDD. Results The study comprised 65 women and seven men (mean age 57.78 ± 8.73 years). Initial HSRs to carboplatin, cisplatin, and oxaliplatin occurred in 38, 13, and 21 patients, respectively. All patients reacted at the fifth (median) recurrent infusions (min:1, max:20). The median values for carboplatin, cisplatin, and oxaliplatin were 6 (1–20), 3 (1–15), and 3 (1–11), respectively. Most initial HSRs were grade 2 (n = 40, 55.6%) and 3 (n = 27, 37.5%); only 6.9% (n = 5) were grade 1. Patients with grade 1, 2, and 3 initial HSRs had positive platin skin test results at rates of 80%, 74%, and 88%, respectively. A total of 232 RDDs were performed in 72 patients and 98.7% of these desensitizations were completed. BTRs occurred in 56 (24.1%) (grade 1 n = 14, 25%; grade 2 n = 32, 57%; grade 3 n = 10, 18%) of these desensitizations. Breakthrough reactions were more severe in patients with positive SPTs or 1:100 or 1:10 dilutions of IDT (p = 0.014). BTR was not observed during RDD in any of the patients with positive 1:1 dilutions of IDT. Positivity on prick or 1:100 or 1:10 IDT increased the risk of BTR 5.058 times. There was no significant association between the risk of BTRs and age, drug cycle, sex, comorbidities, or atopy. Conclusion In our experience, 98.7% of 232 RDDs to platins were completed successfully, showing that RDD was safe and effective. Drug skin test positivity is a potential marker for identifying high-risk patients who will have BTRs during RDDs to platins.

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“…Therefore, risk assessment is especially relevant when considering patient selection for drug challenges in delabelling pathways [4 ▪ ]. Patients with an unfavourable risk assessment are not ideal candidates for a confirmatory drug challenge, and instead, direct RDD might be a more cautious approach in these patients [5 ▪ ].…”

Section: Personalizing Depending On the Endophenotypementioning

confidence: 99%

“…Risk stratification involving specific factors can be crucial in management pathways [24,33–36,44,52]. However, a successful risk assessment strategy should not only consider the severity of the reaction or the results in skin testing but it should bear in mind several essential factors that might contribute with different weights to the out-come [4 ▪ ,5 ▪ ]. These can involve; namely, endophenotype factors like the different in-vivo and in-vitro biomarkers (STs, specific IgE, tryptase, IL-6, or baso-phil activation testing); factors related to the drug or the reactions, such as the severity of the reaction, or the type of drug and the number of culprit drugs involved; exceptional situations like pregnancy, acute infections, critically ill patients, the urgency to receive treatment, or clinical trials; factors related to the access to resources, such as appropriate staffing, multidisciplinaryteam support (including intensive care), standard operating procedures, worst-case scenario recovery plans, or dedicated facilities; factors related to the patient, like comorbidities where exposure might provoke situations beyond medical control; and social factors, such as travel distance to the health centre, level of anxiety, or inclination toward drug challenge vs. RDD [1 ▪▪ ,4 ▪ ,5 ▪ ].…”

Section: Personalizing Depending On the Endophenotypementioning

confidence: 99%

“…Patient-related factors are sometimes over-looked, and yet bearing these in mind is crucial for safety [4 ▪ ,5 ▪ ]. For example, two patients could experience a similar DHR with the same drug, and yet their risk assessment could be completely different as one patient is a young and otherwise healthy patient, whereas the other patient has several comorbidities, such as mastocytosis, uncontrolled asthma, and ischaemic cardiac disease.…”

Section: Personalizing Depending On the Endophenotypementioning

confidence: 99%

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Drug allergy desensitization is not a unique recipe

Madrigal-Burgaleta

Guzman-Melendez

Álvarez-Cuesta

2022

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of reviewDrug desensitization is the only therapeutic option for patients with drug allergies who need to receive the drugs they are allergic to, and it is especially critical in patients with an urgent need for chemotherapy, biologics, or antibiotics, where equally effective alternatives might not be available. However, drug desensitization is not a cookbook where anyone with no experience or specific training can find a general recipe. This review article will approach the singularities that make personalized and highly specialized care essential in this field.Recent findingsDrug desensitization needs to be personalized for each individual patient bearing in mind countless factors. Recent articles have tried to define the optimal resources and the most important factors to account for in personalization. However, drug desensitization is only a tool within the wider management pathway, and we will discuss recent findings in allergy delabelling in chemotherapy, biologics, and antibiotics.SummaryRisk-assessment, delabelling, and desensitization protocols, as a part of wider management pathways, can be adapted locally along with comprehensive and multifactorial risk-management strategies. These high-complexity and high-risk procedures, such as drug desensitization, need to be managed by expert allergists who can provide personalization, innovation, continuous improvement, research, and teaching in expert centres.

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Medical algorithm: Diagnosis and treatment of hypersensitivity reactions to cancer chemotherapy

Cited by 12 publications

References 16 publications

Hypersensitivity reactions to chemotherapy: an EAACI Position Paper

Hypersensitivity reactions to chemotherapy: an EAACI Position Paper

Rapid drug desensitization with platin-based chemotherapy: Analysis of risk factors for breakthrough reactions

Drug allergy desensitization is not a unique recipe

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