Hypersensitivity Reactions to Platinum Agents and Taxanes

AbstractHypersensitivity reactions (HSRs) to chemotherapy agents can present a serious challenge to treating patients with preferred or first-line therapies. Allergic reactions through an immunologic mechanism have been established for platinum and taxane agents, which are used to treat a wide variety of cancers including gynecologic cancers. Platin HSRs typically occur after multiple cycles of chemotherapy, reflecting the development of drug IgE sensitization, while taxane HSRs often occur on first or second exposure. Despite observed differences between platin and taxane HSRs, drug desensitization has been an effective method to reintroduce both chemotherapeutic agents safely. Skin testing is the primary diagnostic tool used to risk-stratify patients after initial HSRs, with more widespread use for platinum agents than taxanes. Different practices exist around the use of skin testing, drug challenge, and choice of desensitization protocol. Here, we review the epidemiology, mechanism, and clinical presentation of HSRs to platinum and taxane agents, as well as key controversies in their evaluation and management.

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Skin testing and drug challenge in the evaluation of drug hypersensitivity reactions

Allergy and Asthma Proceedings ◽

10.2500/aap.2021.42.200091 ◽

2021 ◽

Vol 42 (1) ◽

pp. 16-21 ◽

Cited By ~ 1

Author(s):

Anna R. Wolfson ◽

Aleena Banerji

Keyword(s):

Negative Impact ◽

Skin Testing ◽

Drug Hypersensitivity ◽

Clinical History ◽

Hypersensitivity Reactions ◽

Causative Drug ◽

Care Assessment ◽

Drug Hypersensitivity Reactions ◽

Drug Challenge ◽

Drug Challenges

Immediate hypersensitivity to drugs is characterized by symptoms such as hives, swelling, and wheezing. To prevent a negative impact on care, assessment by an allergist is important. Evaluation requires a clear clinical history, but it is often lacking or vague, which makes a diagnosis difficult. Allergists instead can use skin testing and drug challenge to evaluate drug hypersensitivity reactions, which help the patient and provider understand the causative drug(s) and, more importantly, enables the use of the exonerated drug(s). Although penicillin skin testing is standardized, well described, and widely used, skin testing for most other drugs requires the use of a nonirritating skin testing concentration that can have a low negative predictive value. Drug challenges are the criterion standard for confirming tolerance. The allergist must obtain an in-depth clinical history and then follow with skin testing and/or drug challenges when indicated to determine which drugs can be de-labelled and which should be avoided. In this review, we focused on the evaluation of drug hypersensitivity reactions to antibiotics, perioperative agents, biologics, and chemotherapeutics.

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Successful olaparib desensitization using a novel one-day protocol

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-020-00499-x ◽

2020 ◽

Vol 16 (1) ◽

Author(s):

Rongbo Zhu ◽

Stephen Welch ◽

Hannah Roberts

Keyword(s):

Adverse Reactions ◽

Chemotherapeutic Agents ◽

Hypersensitivity Reactions ◽

Immediate Hypersensitivity ◽

Case Presentation ◽

Tablet Form ◽

Desensitization Protocol ◽

Ige Mediated ◽

Loss Of Tolerance

Abstract Background Olaparib is a revolutionary treatment for patients with ovarian and breast cancer. Currently, there is no established 1-day drug desensitization protocol for patients with olaparib type-1 hypersensitivity reactions despite well documented IgE-mediated adverse reactions occurring with olaparib. Case presentation We report a 58-year-old female with immediate, reproducible IgE-mediated adverse reactions to olaparib tablets with implementation of a 1-day novel desensitization protocol to olaparib. Following desensitization, the patient was successfully transitioned from olaparib capsules to tablets with no loss of tolerance. Conclusions To our knowledge, this is the first reported case of successful olaparib desensitization using a novel 1-day desensitization protocol, and will contribute to drug allergy knowledge, in an area where robust data is lacking. This case demonstrates the important role for drug desensitization in patients with immediate hypersensitivity reactions to chemotherapeutic agents. Furthermore, as olaparib capsules are being phased out in favour of olaparib tablets, we provide a clear case that transitioning from capsule to tablet form did not cause a loss of tolerance.

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Hypersensitivity Reactions Associated with Platinum Antineoplastic Agents: A Systematic Review

Metal-Based Drugs ◽

10.1155/2010/207084 ◽

2010 ◽

Vol 2010 ◽

pp. 1-11 ◽

Cited By ~ 91

Author(s):

Nektaria Makrilia ◽

Ekaterini Syrigou ◽

Ioannis Kaklamanos ◽

Leonidas Manolopoulos ◽

Muhammad Wasif Saif

Keyword(s):

Signs And Symptoms ◽

Skin Tests ◽

Type I ◽

Platinum Compound ◽

Hypersensitivity Reactions ◽

Management Options ◽

Line Setting ◽

Chemotherapy Agents ◽

Platinum Agents ◽

Rule Out

Platinum-containing chemotherapy agents (cisplatin, carboplatin, oxaliplatin) have been approved in the first-line setting of numerous malignancies, such as ovarian, bladder, head and neck, colorectal, and lung cancer. Their extensive use over the last decade has led to a significant increase in the incidence of hypersensitivity reactions, which are defined as unforeseen reactions whose signs and symptoms cannot be explained by the known toxicity of these drugs. Skin rash, flushing, abdominal cramping, itchy palms, and back pain are common symptoms. Cardiovascular and respiratory complications can prove fatal. Multiple pathogenetic mechanisms have been suggested. Hypersensitivity usually appears after multiple infusions, suggesting type I allergic reactions; however, other types of hypersensitivity also seem to be implicated. Several management options are available to treating physicians: discontinuation of chemotherapy, premedication, prolonging of infusion duration, desensitization protocols, and replacement with a different platinum compound after performing skin tests that rule out cross-reactions among platinum agents.

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Immediate reaction to ibrutinib amenable to oral desensitization

Journal of Oncology Pharmacy Practice ◽

10.1177/10781552211004689 ◽

2021 ◽

pp. 107815522110046

Author(s):

Neelam A Phadke ◽

Samantha O Luk ◽

Ephraim P Hochberg ◽

Aleena Banerji

Keyword(s):

Maculopapular Rash ◽

Chemotherapeutic Agents ◽

Lymphocytic Leukemia ◽

Hypersensitivity Reactions ◽

First Line ◽

Management Guidelines ◽

Cutaneous Hypersensitivity ◽

Ige Mediated ◽

To Receive ◽

Oral Desensitization

Introduction Although up to half of patients receiving chemotherapeutic agents develop hypersensitivity reactions to the same, desensitization protocols can induce temporary tolerance to allow patients to continue to receive first-line treatment. Approximately 25% of patients develop cutaneous hypersensitivity reactions to ibrutinib, but there are no published management guidelines. Case report We describe the case of a 71-year-old woman with chronic lymphocytic leukemia who developed a delayed maculopapular rash with lip tingling and swelling following ibrutinib therapy. Management and outcome We performed a novel 11-step desensitization procedure to ibrutinib allowing us to successfully induce tolerance against IgE-mediated symptoms in this patient. Discussion As indications for ibrutinib use expand and more patients present with IgE-mediated symptoms, we expect that this protocol will provide benefit for many such patients.

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PATTERNS OF RESPONSE AND DRUGS INVOLVED IN HYPERSENSITIVITY REACTIONS TO BETA-LACTAMS IN CHILDREN.

10.22541/au.161635658.84094563/v1 ◽

2021 ◽

Author(s):

Isabel Torres-Rojas ◽

Diana Perez ◽

Maria Luisa Somoza-Alvarez ◽

Elisa Haroun Diaz ◽

Ana María Prieto-Moreno Pfeifer ◽

...

Keyword(s):

Clavulanic Acid ◽

Skin Testing ◽

Drug Hypersensitivity ◽

Penicillin G ◽

Hypersensitivity Reactions ◽

Beta Lactams ◽

Provocation Tests ◽

Drug Challenge ◽

Immediate Reactions

Background Beta-lactams generate different allergenic determinants that induce selective or cross-reactive drug hypersensitivity reactions (DHRs). We aimed to identify the drugs involved, the selectivity of the response, the mechanism, and the value of the different diagnostic tests for establishing a diagnosis in children evaluated for DHRs to beta-lactams. Methods Prospective study evaluating children aged under 16 years reporting DHRs to beta-lactams. Reactions were classified as immediate and nonimmediate reactions. The work-up included sIgE, skin testing and drug provocation tests (DPTs) for immediate reactions and patch testing and DPTs for nonimmediate ones. Results Of the 510 included children, 133 were evaluated for immediate reactions and confirmed in 8.3%. Skin test/in vitro IgE contributed to diagnosing half of the cases. Selective reactions occurred with amoxicillin (63%), followed by common penicillin determinants (27%) and cephalosporins (0.9%). Among nonimmediate reactions (11,4% of the 377 children evaluated), most required DPTs, 52.7% of which were positive at 6–7 days of drug challenge. Selective reactions were identified with amoxicillin (80%), penicillin G (7.5%), cephalosporins (7.5%), and clavulanic acid (5%). Urticaria and maculopapular exanthema were the most frequent entities. Conclusions There were few confirmed cases of either type of reaction. Skin testing proved less valuable in nonimmediate reactions, over half of which would also have been lost in a short DPT protocol. Selective responders to amoxicillin were more likely to have nonimmediate reactions, while clavulanic acid-selectivity was exclusive to the nonimmediate typology. Over half the cases with DPTs required 6-7 days of treatment for DHR confirmation.

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A new desensitization protocol, overcoming hypersensitivity reactions to chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e15523 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e15523-e15523

Author(s):

Andrei Dan Havasi ◽

Calin Ioan Cainap ◽

Ioan-Cătălin Vlad ◽

Patriciu Achimaş-Cadariu ◽

Daniel Genel Sur ◽

...

Keyword(s):

Allergic Reaction ◽

Chemotherapeutic Agents ◽

Hypersensitivity Reactions ◽

Chemotherapy Administration ◽

Desensitization Protocol ◽

Optimal Approach ◽

A Prospective Study ◽

Rate Of Failure ◽

Administration Methods ◽

Responsible Drug

e15523 Background: Despite the progress for cancer treatment, some drugs remain a cornerstone for an optimal approach. Hypersensitivity reactions to chemotherapy may render these essential chemotherapeutic agents useless and for some types of cancer continuing the therapeutic scheme could be crucial. Various regimens for desensitization to allow chemotherapy administration through the time were conceived, with different dilutions, time and settings of administration. Methods: A prospective study of patients with systemic treatment for histopathologically confirmed cancer in our Oncological Institute „Prof. Ion Chiricuta” Cluj-Napoca, with an allergic reaction during treatment being the keys inclusion criteria in the analysis. Patients were administered a three days desensitization regimen from the following cycle of treatment with blood samples that were taken to observe the predictive value of biological markers. Results: Eighty-two patients were the initial pool, with a median age of 56 years. Platin derivates containing regiments were responsible for an allergic reaction for 75 out of 82 patients. Four of them were known with a previous allergic reaction for chemotherapy in their personal medical history, and 56 of them had more than one chemotherapy line in their treatment. More than 688 desensitization cycles were administrated during our study with a rate of failure of 1.3 %. The main reason for discontinuation was disease progression or adjuvant character (limited duration) of the chemotherapy administration. Conclusions: Allergic reaction does not impede the administration of the responsible drug. A 3-day inpatient regimen could be a valuable option with a successful rate of administration without the need for ICU monitoring.

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162. Assessment of Beta-lactam Allergies as Rationale for Receipt of Vancomycin for Surgical Prophylaxis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.207 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S90-S90

Author(s):

Kendall J Tucker ◽

YoungYoon Ham ◽

Haley K Holmer ◽

Caitlin M McCracken ◽

Ellie Sukerman ◽

...

Keyword(s):

Antimicrobial Prophylaxis ◽

Skin Testing ◽

Cross Reactivity ◽

Penicillin Allergy ◽

Beta Lactam ◽

First Line ◽

Surgical Prophylaxis ◽

Inappropriate Use ◽

Oral Amoxicillin ◽

Ige Mediated

Abstract Background Beta-lactam (BL) antibiotics are first-line agents for most patients receiving antimicrobial prophylaxis in surgical procedures. Despite evidence showing low cross-reactivity between classes of BLs, patients with allergies commonly receive vancomycin as an alternative to avoid allergic reaction. The objective of this study was to identify potentially inappropriate use of vancomycin surgical prophylaxis among patients with reported BL allergies. Methods Adult patients (≥18 years) receiving vancomycin for surgical prophylaxis with a reported penicillin and/or cephalosporin allergy at our institution between August 2017 to July 2018 were retrospectively evaluated for potential eligibility for penicillin allergy testing and/or receipt of standard prophylaxis. Surgery type and allergy history were extracted from the electronic medical record. Per our institution’s penicillin-testing protocol, patients with IgE-mediated reactions < 10 years ago were eligible for penicillin skin testing (PST), mild reactions or IgE-mediated reaction > 10 years ago were eligible for direct oral amoxicillin challenge, and severe non-IgE mediated allergies were ineligible for penicillin allergy evaluation or BL prophylaxis. Results Among 830 patients who received vancomycin for surgical prophylaxis, 196 reported BL allergy and were included in the analysis (155 with penicillin allergy alone; 21 with cephalosporin allergy; 20 with both cephalosporin and penicillin allergy). Approximately 40% of surgeries were orthopedic. Six patients were ineligible for BL prophylaxis. Per institutional protocol, 73 of 155 patients (48%) may have qualified for PST; 81 of 155 (52%) patients may have received a direct oral amoxicillin challenge. Only 3 of 22 patients with history of methicillin-resistant Staphylococcus aureus appropriately received additional prophylaxis with vancomycin and a BL. Conclusion Patients with BL allergies often qualify for receipt of a first-line BL antibiotic. An opportunity exists for improved BL allergy assessment as an antimicrobial stewardship intervention. Future studies should evaluate outcomes associated with BL allergy evaluation and delabeling in patients receiving surgical prophylaxis. Disclosures All Authors: No reported disclosures

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Immediate hypersensitivity reaction followed by successful oral desensitization to ursodiol

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-021-00578-7 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Erika Yue Lee ◽

Christine Song

Keyword(s):

Hypersensitivity Reaction ◽

Primary Biliary Cholangitis ◽

Line Treatment ◽

Second Line ◽

Immediate Hypersensitivity ◽

First Line ◽

Case Presentation ◽

Desensitization Protocol ◽

First Line Treatment ◽

Oral Desensitization

Abstract Background Immediate hypersensitivity reaction to ursodiol is rare and there is no previously published protocol on ursodiol desensitization. Case presentation A 59-year-old woman with primary biliary cholangitis (PBC) developed an immediate hypersensitivity reaction to ursodiol—the first-line treatment for PBC. When she switched to a second-line treatment, her PBC continued to progress. As such, she completed a novel 12-step desensitization protocol to oral ursodiol. She experienced recurrent pruritus after each dose following desensitization, which subsided after a month of being on daily ursodiol. Conclusion Immediate hypersensitivity reaction to ursodiol is uncommon. Our case demonstrated that this novel desensitization protocol to ursodiol could be safely implemented when alternative options are not available or have proven inferior in efficacy.

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Real world cost and health outcomes of patients presented with chest pain in England: which is the most cost-effective first-line test?

European Heart Journal ◽

10.1093/ehjci/ehaa946.3547 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Tsiachristas ◽

H West ◽

E.K Oikonomou ◽

B Mihaylova ◽

N Sabharwall ◽

...

Keyword(s):

Chest Pain ◽

Health Outcomes ◽

Diagnostic Tests ◽

Clinical Presentation ◽

Cost Effective ◽

Funding Source ◽

First Line ◽

Nice Guidelines ◽

Exercise Ecg ◽

Stable Chest Pain

Abstract Background The National Institute for Health and Care Excellence (NICE) updated their guidance for the management of patients with stable chest pain and recommended that all patients undergo computed tomography coronary angiography (CTCA). This update has sparked a great deal of debate, and was followed by upgrade of CTCA into a Class I indication in the recent ESC guidelines. The cost-effectiveness of using CTCA as first line investigation is still unclear. Purpose To describe the current clinical pathway of patients with stable chest pain presented to outpatient clinics, assess the compliance with the updated NICE guideline, and explore the costs and health outcomes of different non-invasive diagnostic tests in real-world clinical setting. Methods We used data of 4,297 patients who attended chest pain clinics in Oxford between 1 January 2014 and 31 July 2018. Data included clinical presentation (e.g. age and previous cardiovascular conditions), diagnostic tests, outpatient visits, hospitalization, and hospital mortality and was compared between 6 alternative first-line diagnostic tests. Multinomial regressions were performed to estimate the probability of receiving each alternative and the associated cost after adjusting for clinical presentation. A decision tree was developed to describe the clinical pathway for each alternative first-line diagnostic in terms of subsequent diagnostic tests and treatments and to estimate the associated costs and life days. Results The proportion of patients who received CTCA as first line diagnostic test increased from 1% in 2014 to 17% in 2018, while the publication of the updated NICE guidelines in 2016 led to a threefold increase in this proportion. CTCA is less likely to be provided as a first-line diagnostic to patients who are younger age, males, smokers, and have angina, PVD, or diabetes. The standardised rate of hospital admission was the lowest in the exercise ECG cohort (0.35 admissions per 1,000 life-days) followed by the CTCA cohort (0.40 admissions per 1,000 life-days) while the latter cohort had the lowest standardised rate of cardiovascular treatment (2.74% per 1,000 life days). Stress echocardiography and MPS were associated with higher costs compared with CTCA, other ECG, and exercise ECG after adjusting for clinical presentation and days of follow-up. CTCA is the pathway most likely to be cost-effective, even compared to exercise ECG, while the other diagnostic alternatives are dominated (i.e. they cost more for less life-days). Conclusions Currently, the updated NICE guidelines for stable chest pain are implemented only to a fifth of the cases in England. Our findings support existing evidence that CTCA is the most-cost effective first-line diagnostic test for this population. Hopefully, this will inform the debate around the implementation of the guidelines and help commissioning and clinical decision processes worldwide. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institute of Health Research Oxford Biomedical Research Centre

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The complexities of insulin allergy: a case and approach

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-021-00554-1 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Babak Aberumand ◽

Samira Jeimy

Keyword(s):

Skin Testing ◽

Emergency Department Visits ◽

Good Effect ◽

First Episode ◽

Similar Reaction ◽

Hypersensitivity Reactions ◽

Epinephrine Administration ◽

Insulin Allergy ◽

Recombinant Insulin ◽

Insulin Dependent

Abstract Background Insulin hypersensitivity is rare, but challenging for individuals with diabetes. The prevalence of insulin allergy has decreased since the introduction of human recombinant insulin preparations. Hypersensitivity reactions range from injection site erythema and swelling, to anaphylaxis. While some reactions are to excipients (zinc, protamine, metacresol), many are to recombinant insulin itself. We present a case of type 1 hypersensitivity to various preparations of insulin in a patient with insulin-dependent type 2 diabetes mellitus (T2DM). Case presentation A 61-year-old woman with a 30-year history of insulin-dependent T2DM was referred for evaluation of reactions to insulin. She had two episodes over 5-months; both required Emergency Department visits and epinephrine administration. The first episode entailed a burning sensation of the extremities and nausea, immediately after injecting NovoRapid® insulin. The second event entailed a similar reaction but this time there was also angioedema of the upper airway with difficulty breathing and hypotension, immediately after injecting Levemir® and NovoRapid®, and taking metformin. There were no cofactors such as exercise, infectious illness, or NSAIDs use. Skin testing was performed with metformin, Lantus®, Humalog®, NovoRapid®, glulisine, insulin regular, NPH, Levemir® and the excipient protamine, as per published testing concentrations. Metacresol was not tested as its use was restricted by the hospital pharmacy. Insulin preparations with and without metacresol were included in testing however. A clinic staff served as a negative control. The patent had negative testing with protamine, but sensitization to all insulin preparations. Metformin skin testing and challenge along with latex IgE were negative. Subsequently, she underwent intentional weight loss of 70 lb, and was started on oral hypoglycemics with good effect. Conclusions Our case highlights the importance of diagnosing insulin allergy through a detailed history and focused testing. Therapeutic strategies include avoidance and insulin alternatives, alternate insulin preparations, or desensitization. In severe recurrent hypersensitivity reactions, Omalizumab or pancreatic transplantation have been effective.

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