Hypersensitivity Reactions to Taxanes: A Comprehensive and Systematic Review of the Efficacy and Safety of Desensitization

Villarreal-González, Rosalaura Virginia; González-Díaz, Sandra; Vidal-Gutiérrez, Oscar; Canel-Paredes, Alejandra; de la Cruz-de la Cruz, Carlos; García-Campa, Mariano; López-Méndez, Alfonso; Alvarado-Ruiz, Sofía; Castells, Mariana

doi:10.1007/s12016-023-08968-y

Cited by 2 publications

(2 citation statements)

References 66 publications

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“…Various personalized desensitization protocols still allow cancer patients to continue taxane-and platinum-based chemotherapy after iHSR occurrence, avoiding the need to resort to other less effective or more toxic therapeutic approaches [12,14,15]. The choice of appropriate drug desensitization protocols in drug allergies is routinely based on iHSR severity grading, skin tests (STs), and laboratory tests, including serum-specific IgE assays and the basophil activation test (BAT) [16,17].…”

Section: Introductionmentioning

confidence: 99%

A Modified Basophil Activation Test for the Clinical Management of Immediate Hypersensitivity Reactions to Paclitaxel: A Proof-of-Concept Study

La Sorda,

Fossati,

Graffeo

et al. 2023

Cancers

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Immediate hypersensitivity reactions (iHSRs) to taxanes are observed in 6% and 4% of gynecologic and breast cancer patients, respectively. Drug desensitization is the only option, as no comparable alternative therapy is available. Surfactants in the taxane formulation have been implicated in the immunopathogenesis of iHSRs, although sporadic skin test (ST) positivity and iHSRs to nab-paclitaxel have suggested the involvement of the taxane moiety and/or IgE-mediated pathomechanisms. In vitro diagnostic tests might offer insights into mechanisms underlying iHSRs to taxanes. The aim of the present study was to address this unmet need by developing a novel basophil activation test (BAT). The study included patients (n = 31) undergoing paclitaxel/carboplatin therapy. Seventeen patients presented with iHSRs to paclitaxel (iHSR-Taxpos), and eleven were tolerant (iHSR-Taxneg). Fourteen patients presented with iHSRs to carboplatin (iHSR-Plpos), and fourteen were tolerant (iHSR-Plneg). The BAT median stimulation index (SI) values were 1.563 (range, 0.02–4.11; n = 11) and −0.28 (range −4.88–0.07, n = 11) in iHSR-Taxpos and iHSR-Taxneg, respectively. The BAT median SI values were 4.45 (range, 0.1–26.7; n = 14) and 0 (range, −0.51–1.65; n = 12) in iHSR-Plpos and iHSR-Plneg, respectively. SI levels were not associated with iHSR severity grading. Comparing BAT results in iHSR-Taxpos and iHSR-Taxneg showed the area under the receiver operator characteristic (ROC) curve to be 0.9752 (p = 0.0002). The cutoff calculated by the maximized likelihood ratio identified 90.91% of iHSR-Taxpos patients and 90.91% of iHSR-Taxneg patients. Comparing BAT results for iHSR-Plpos and iHSR-Plneg showed the area under the ROC curve to be 0.9286 (p = 0.0002). The cutoff calculated by the maximized likelihood ratio identified 78.57% of iHSR-Plpos patients and 91.67% of iHSR-Plneg patients. Most iHSR-Taxpos patients for which ST was available (10/11) scored ST-negative and BAT-positive, whereas most iHSR-Plpos patients for which ST was available (14/14) scored both BAT- and ST-positive. This suggested the intervention of non-IgE-mediated mechanisms in iHSR-Taxpos patients. Consistent with this view, an in silico molecular docking analysis predicted the high affinity of paclitaxel to the degranulation-competent MRGPRX2 receptor. This hypothesis warrants further in vitro investigations. In conclusion, the present study provides preliminary proof-of-concept evidence that this novel BAT has potential utility in understanding mechanisms underlying iHSRs to taxanes.

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Section: Introductionmentioning

confidence: 99%

A Modified Basophil Activation Test for the Clinical Management of Immediate Hypersensitivity Reactions to Paclitaxel: A Proof-of-Concept Study

La Sorda,

Fossati,

Graffeo

et al. 2023

Cancers

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show abstract

“…Efforts have been made for decades through various studies to understand and overcome taxane allergies. 1 Immediate HSR caused by taxanes can be summarized into 3 main pathways: 1) specific antibody (immunoglobulin E [IgE]/immunoglobulin G [IgG])-mediated activation of mast cells or basophils, which can be initiated by either taxane moiety or the solubilizer (Cremophor) added to the medication, 2) direct activation of basophils by taxanes without IgE-mediated pathway, and 3) anaphylatoxins (C3a and C5a) produced by an IgG-mediated mechanism that triggers complement activation through the creation of immune complexes. These anaphylatoxins can then activate mast cells and basophils via their surface receptors.…”

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confidence: 99%

Understanding and Challenging of Taxane Hypersensitivity

Park

2024

Allergy Asthma Immunol Res

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Hypersensitivity Reactions to Taxanes: A Comprehensive and Systematic Review of the Efficacy and Safety of Desensitization

Cited by 2 publications

References 66 publications

A Modified Basophil Activation Test for the Clinical Management of Immediate Hypersensitivity Reactions to Paclitaxel: A Proof-of-Concept Study

A Modified Basophil Activation Test for the Clinical Management of Immediate Hypersensitivity Reactions to Paclitaxel: A Proof-of-Concept Study

Understanding and Challenging of Taxane Hypersensitivity

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