Hypersensitivity reactions to mAbs: 105 desensitizations in 23 patients, from evaluation to treatment

Brennan, Patrick J.; Bouza, Tito Rodriguez; Hsu, Florence Ida; Sloane, David E. E.; Castells, Mariana

doi:10.1016/j.jaci.2009.09.009

Cited by 236 publications

(280 citation statements)

References 47 publications

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“…Rapid desensitization is the induction of temporary clinical tolerance to a drug, thereby allowing the patient to be treated with the medication, which had caused hypersensitivity reaction (Brennan et al 2009;Castells 2006a, b;Castells et al 2012;Liu et al 2011). Rapid desensitization targets mast cells so that it can be used for IgE-mediated anaphylactic or (non-IgE-mediated) anaphylactoid immediate type reactions (Liu et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Rapid Desensitization for Immediate Hypersensitivity to Galsulfase Therapy in Patients with MPS VI

et al. 2016

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Mucopolysaccharidosis type VI (MPS VI) is a progressive, chronic, and multisystem lysosomal storage disease. Enzyme replacement therapy (ERT) with the recombinant human arylsulfatase B enzyme (galsulfase [Naglazyme]) is recommended as first-line therapy. It is generally reported as safe and well tolerated. Frequently observed mild to moderate infusion-related reactions which can be easily handled by reducing or interrupting the infusion and/or administering additional antihistamines, antipyretics, and corticosteroids are mostly mediated by non-IgE mechanisms. Here we report two children with MPS VI who experienced IgE-mediated reactions with galsulfase at the second year of the therapy. One child had anaphylaxis and the other had urticarial eruptions. They could receive ERT after successful rapid desensitization. To our knowledge, this is the second report on galsulfase allergy with IgE-mediated reaction. It is important to recognize IgE-mediated reactions since they can be lifethreatening and do not respond to the standard therapies.We recommend allergy skin tests in the evaluation of infusion-related reactions unresponsive to standard therapies, so that continuation of ERT will be feasible after successful desensitization. Abbreviations BWHBrigham and Women's Hospital ERT Enzyme replacement therapy GAG Glycosaminoglycan MPS VI Mucopolysaccharidosis type VI N-acetylgalactosamine -4-sulfatase

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Section: Discussionmentioning

confidence: 99%

Rapid Desensitization for Immediate Hypersensitivity to Galsulfase Therapy in Patients with MPS VI

et al. 2016

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“…Reported reactions to mAbs include urticarial rash, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, and acute respiratory distress. 1 The exact mechanism of HSRs to mAbs is not fully understood. [1][2][3] While sensitization typically occurs with repeated exposure, there are reports of reactions after the first infusion of mAbs; hence, at least some of the immediate HSRs may be caused by drug-induced cytokine release.…”

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confidence: 99%

“…1 The exact mechanism of HSRs to mAbs is not fully understood. [1][2][3] While sensitization typically occurs with repeated exposure, there are reports of reactions after the first infusion of mAbs; hence, at least some of the immediate HSRs may be caused by drug-induced cytokine release. 1,4 When treatment options are limited, rapid desensitization, also referred to as temporary induction of tolerance, should be considered to allow for continued use of these drugs in patients with a history of HSRs.…”

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confidence: 99%

“…[1][2][3] While sensitization typically occurs with repeated exposure, there are reports of reactions after the first infusion of mAbs; hence, at least some of the immediate HSRs may be caused by drug-induced cytokine release. 1,4 When treatment options are limited, rapid desensitization, also referred to as temporary induction of tolerance, should be considered to allow for continued use of these drugs in patients with a history of HSRs. While HSRs and desensitization to mAbs have been well described in adults, [1][2][3] to our knowledge, the experience in children is limited to only two case reports, including only one to rituximab.…”

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confidence: 99%

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Rituximab Desensitization in Pediatric Patients: Results of a Case Series

Dilley

Lee

Platt

et al. 2016

Pediatric Allergy, Immunology, and Pulmonology

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Rituximab is a monoclonal antibody (mAb) primarily used to treat oncologic and autoinflammatory conditions. Although hypersensitivity reactions (HSRs) and desensitization protocols to mAbs have been well described in adults, the experience in the pediatric population is very limited. We sought to determine the safety and efficacy of desensitization to rituximab in the pediatric population at our institution. We retrospectively reviewed the experience with HSRs and desensitization to rituximab during a 5-year period in our tertiary care pediatric center, including reaction evaluation, premedication regimens, and desensitization procedures and protocols. A total of 17 desensitizations to rituximab were performed in three patients. A 14-year-old patient underwent successful desensitization to rituximab using a published adult protocol without incident. Two younger patients (ages 7 years and 23 months) experienced significant reactions during initial desensitization attempts. Therefore, we designed a modified desensitization protocol to rituximab, with particular attention to the rate of infusion as mg/kg/h. This new patient weight-based protocol was successfully used in a total of 13 desensitizations in these two patients. Desensitization to rituximab was a safe and effective procedure in our pediatric population. We present a new patient weight-based desensitization protocol for pediatric patients who develop HSRs to rituximab, with particular usefulness for younger pediatric patients and potential utility in pediatric patients with HSRs to other mAbs.

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with N-formylmethionyl-leucyl-phenylalanine, anti-IgE antibody, or allergens [4,5]. The expression can be detected efficiently by flow cytometry.

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confidence: 99%

Localized insulin‐derived amyloidosis: A potential pitfall in the diagnosis of systemic amyloidosis by fat aspirate

et al. 2012

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with N-formylmethionyl-leucyl-phenylalanine, anti-IgE antibody, or allergens [4,5]. The expression can be detected efficiently by flow cytometry. We report our experience with the ADR following rituximab therapy in a group of 18 patients (M:8; F:10, age range: 36-85) affected by lymphoproliferative diseases, according to the WHO classification. Patients received a standard dose of rituximab (375 mg/m 2 ) combined with cyclophosphamide, vincristine, and prednisone or cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. On average, each patient received 4.5 infusions of rituximab (median, the number of infusions range between 2 and 8). Before rituximab infusion, a premedication using diphenhydramine (10 mg), dexamethasone (8 mg intravenous (IV)), and ranitidine (100 mg IV) was given to the patients. The following major ADR were reported in five patients: urticaria, hypotension, angioedema, and bronchospasms. The reactions required medical intervention and discontinuation of the infusion. Within one year from the reactions, the BAT was performed on all patients. To assess the rituximab challenge, different concentrations, spanning several log scales, and mimicking in vivo concentrations, 0.25 and 0.50 lg/lL (i.e., 250 and 500 lg/mL) were evaluated. Two other higher concentrations 1.00 and 2.00 lg/lL, which do not represent therapeutic concentrations, were used to verify if these high concentrations are still able to elicit maximal stimulation. The test was then carried out in 18 healthy subjects to see if rituximab was able to stimulate the basophils of normal individuals. This was done to exclude the presence of nonspecific stimulatory components such as preservatives or the ability of rituximab to elicit nonspecific activation. At two doses corresponding to ''in vivo'' concentrations of rituximab, mean ± standard deviation (SD) percentage of CD631 basophils was higher in patients with ADR compared to those without, (6.75 ± 3.79 vs. 1.92 ± 1.16, P < 0.001; 6.86 ± 5.60 vs. 2.20 ± 1.33, P < 0.05, respectively). At 1.00 and 2.00 lg/lL, there were differences for all pairwise comparisons (P < 0.05; Fig. 1). No significant differences were obtained in patients without reactions and in the healthy subjects. The dose finding in our study showed that the maximal basophil reactivity is obtained using two concentrations of rituximab, 0.25 and 0.50 lg/lL, that represent those to be considered ''optimal,'' as they discriminate between patients and control individuals, eliciting maximal stimulation.Further studies with a larger number of patients are required, but from the data so far available it would seem that the CD63 BAT could be very useful in evaluating patients suspected of being hypersensitive to rituximab, mainly in the absence of other diagnostic tests. Localized insulin-derived amyloidosis: A potential pitfall in the diagnosis of systemic amyloidosis by fat aspirateTo the Editor: Accurate amyloid subtyping is critical after diagnosing amyloidosis as treatment can vary from observation to chemoth...

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Hypersensitivity reactions to mAbs: 105 desensitizations in 23 patients, from evaluation to treatment

Cited by 236 publications

References 47 publications

Rapid Desensitization for Immediate Hypersensitivity to Galsulfase Therapy in Patients with MPS VI

Rapid Desensitization for Immediate Hypersensitivity to Galsulfase Therapy in Patients with MPS VI

Rituximab Desensitization in Pediatric Patients: Results of a Case Series

Localized insulin‐derived amyloidosis: A potential pitfall in the diagnosis of systemic amyloidosis by fat aspirate

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