Delabeling Patients from Chemotherapy and Biologics Allergy: Implementing Drug Provocation Testing (original) (raw)
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J Allergy Clin Immunol Pract , 2019
BACKGROUND: Large-scale studies of drug provocation testing (DPT) or rapid drug desensitization (RDD) for hypersensitivity to antineoplastics and biologicals are scarce and limited to a few institutions. OBJECTIVE: Our aim was to review our experience with DPT and RDD in a large number of patients with a history of hypersensitivity to antineoplastics and biologicals and summarize the practical implications of that experience. METHODS: This was a 7-year prospective, observational, longitudinal study with reactive patients referred to the Desensitization Program at Ramon y Cajal University Hospital (RCUH). Patients were selected after following our systematic and validated diagnostic approach (clinical history, skin test, risk assessment, specific IgE, DPT) before RDD. Candidate patients underwent RDD using the RCUH protocol. Cetuximab reactors underwent 1-bag RDDs. RESULTS: A total of 1027 intravenous RDDs were performed using the RCUH protocol (399 platins, 395 taxanes, 178 biologicals, 55 other drugs), and 1026 were successfully accomplished in the 186 patients (of 515 referred patients) who met inclusion criteria for RDD. No breakthrough reactions occurred in 88% of RDDs. Most breakthrough reactions were mild. A total of 341 DPTs were performed, and 229 results were negative (67%). DPTs helped exclude hypersensitivity in 44% (229 of 515) of referred patients. In addition, 77 one-bag RDDs were performed in 6 cetuximab-reactive patients. CONCLUSIONS: This experience allows us to describe general management plans, as well as specific patient phenotypic patterns, predictors for reactions, and risk considerations that need a tailored approach (taking into account the 3 prominent drug categories: platins, taxanes, and biologicals).
Frontiers in Allergy, 2022
The increased use of antineoplastic drugs has been associated with a rising number of hypersensitivity reactions to these drugs, which has led to a growth in the demand for assistance from allergy services. The involvement of an allergist is essential to ensure that these patients with hypersensitivity reactions continue to be able to receive appropriate first-line treatment. Chemotherapy and biological agents have specific handling requirements and all the allergy departments involved in the diagnosis and therapeutic management of patients reacting to these drugs should find the means to guarantee safety. There are currently several guidelines on the safe handling of hazardous drugs for healthcare workers. However, specific recommendations are lacking for reducing occupational exposure in staff working in the allergy departments and managing these drugs for the diagnosis and management of hypersensitivity reactions. This review article focuses on the safe handling strategy of the a...
Adverse reactions during drug challenges: a single US institution's experience
Annals of Allergy, Asthma & Immunology, 2013
Background: Drug challenge is a useful tool when diagnostic testing lacks predictive value for a questionable history of drug allergy. Placebo-controlled drug challenge studies demonstrate that a significant number of patients report purely subjective symptoms to placebo. Objective: To evaluate the safety and rate of adverse effects when performing drug challenges and to identify predictive factors for occurrences of subjective symptoms during drug challenges. Methods: We performed a 6-year, retrospective medical record review of patients who underwent drug challenges by members of the Allergy and Immunology Division after consultation deemed drug challenges to be appropriate. Statistical analysis was performed to compare the proportion of patients with subjective symptoms based on certain factors, including sex, age, number of listed drug allergies, interval from historical drug reaction to the drug challenge, and types of historical reaction. Results: A total of 114 patients underwent 123 drug challenges. Only 1 patient was deemed to have a true positive drug challenge result. Twenty patients reported subjective symptoms during graded challenge, all of which were not deemed a positive challenge. There was a significantly higher proportion of patients who reported subjective symptoms in females, those with a higher number of listed drug allergies, and those whose historical reactions were primarily subjective in nature. Conclusion: Drug challenges are safe procedures in appropriately selected patients. A number of patients report subjective symptoms during drug challenges. Identifying patients at high risk for subjective symptoms may assist in determining whether placebo-controlled drug challenges should be performed.
Journal of Allergy and Clinical Immunology, 2008
Hypersensitivity reactions (HSRs) to chemotherapeutic drugs, including mAbs, often require that the provoking medication be discontinued, thus raising a dilemma for the caregiver: further use could precipitate a severe, even fatal, allergic reaction on re-exposure, but alternative drugs might be poorly tolerated or much less effective compared with the preferred agent.We have developed a standardized rapid desensitization protocol for achieving temporary tolerization to drug allergens. In this study we evaluate the safety and efficacy of this protocol.Ninety-eight patients who had HSRs in response to treatment with carboplatin, cisplatin, oxaliplatin, paclitaxel, liposomal doxorubicin, doxorubicin, or rituximab received rapid desensitization to these agents. A standardized 12-step protocol was used, with treatment given intravenously or intraperitoneally. Initial desensitizations occurred in the medical intensive care unit, whereas most subsequent infusions took place in an outpatient setting. Safety and efficacy of the protocol were assessed by review of treatment records.Of the 413 desensitizations performed, 94% induced mild or no reactions. No life-threatening HSRs or deaths occurred during the procedure, and all patients received their full target dose. Most reactions occurred during the first desensitization. Reactions were most commonly reported at the last step of the protocol. Desensitizations through the intravenous and intraperitoneal routes were equally effective.Our standardized 12-step protocol for rapid drug desensitization is safe and effective and has been adopted as the standard of care at our institutions in treating patients with HSRs to chemotherapeutic drugs, including mAbs.
Clinical value of in vitro tests for the management of severe drug hypersensitivity reactions
Asia Pacific Allergy
Drug hypersensitivity reactions (DHRs) occasionally present with severe cutaneous adverse reactions (SCARs) which result in a high risk of morbidity and mortality. Although SCARs are rare, the occurrence could lead to a significant increase in healthcare and economic burden, especially when more than one possible culprit drug is implicated. Therefore, the accurate identification of the culprit drug(s) is important for correct labeling and subsequent patient education and avoidance. To date, clinical evaluation using causality assessment has limitations because the assessment may be inaccurate due to the overlapping timelines when multiple drugs are initiated/continued. Moreover, drug provocation tests (DPTs) which is the gold standard in diagnosis, are contraindicated, and in vivo skin tests may also be associated with risks of triggering SCAR. The European Network for Drug Allergy recommended that in vitro tests, if available, should be performed before any in vivo tests. Basophil activation tests and lymphocyte transformation tests, could serve as reliable in vitro tests for both immediate and delayed-type DHR. Many academic medical centers with affiliated laboratory services offer these tests in the diagnostic evaluation of SCARs in clinical practice. This not only complements identification of the culprit drug(s), but may also be used to test for potentially non cross-reactive alternatives, hence avoiding DPTs. In this review, we summarize the roles of in vitro tests in identifying the culprit drug(s) in SCARs, issues with utilization and interpretation of test results, and our experience in clinical practice.
Rapid Desensitization for Hypersensitivity Reactions to Chemotherapeutic Drugs; A Case Series
Iranian Journal of Pharmaceutical Research : IJPR, 2019
Usage of cancer chemotherapeutics drugs can be associated with adverse drug reactions. When IgE-mediated drug reactions are formed following administration of a chemotherapeutics drug that is a drug of choice, drug desensitization protocols can be helpful. HSR can be allergic or nonallergic, but the clinical manifestations are similar. RDD is effective when used appropriately, however it is often over utilized instead of performing a drug challenge. RDD is both an acceptable approach and a high-risk treatment modality in patients, in whom the offending agent is the first choice in chemotherapy. The safety of this modality has been acceptable in large studies. The side effects are often less frequent and less severe by repeating the protocol. We present 4 cases of successful desensitization in cancer patients, who have developed IgE- mediated reactions to their major chemotherapy drug.
BioDrugs, 2013
Hypersensitivity reactions to monoclonal antibodies and chemotherapy, which may vary in severity from mild to life-threatening, can lead to their discontinuation and replacement by alternative agents that are often less effective, more toxic, and/or more expensive. Drug desensitization has emerged as the best treatment modality capable of allowing re-introduction of the hypersensitivity reaction-inducing medication in highly sensitized patients in need of first line therapies. In recent years, the availability of new anti-neoplastic drugs and therapeutic monoclonal antibodies has increased, as has the potential for hypersensitivity reactions. Development of desensitization protocols for these new medications requires a careful assessment of the potential risks and benefits. The purposes of this review are to provide an overview of the presentation of hypersensitivity reactions amenable to desensitization and to increase awareness of the indications for and outcomes of desensitization protocols. Rapid drug desensitization has proven to be a safe and effective way of administering first line therapy to patients with hypersensitivity reactions, providing an extremely powerful treatment modality for patients for whom alternative drugs are deemed unacceptable. Rapid drug desensitization protocols should be administered only by highly trained allergists and nurses who have experience in determining which reactions are amenable to desensitization, and can identify high risk patients and provide them with appropriate care. Efforts should be made to increase awareness of the remarkable safety and efficacy of rapid drug desensitization among non-allergists, especially in the fields of oncology and rheumatology, so as to favor its universal application. Development of desensitization units to provide state-of-the-art care is possible only through coordinated teamwork.