Rapid estimation of whole blood everolimus concentrations using architect sirolimus immunoassay and mathematical equations: comparison with everolimus values determined by liquid chromatography/mass spectrometry

Dasgupta, Amitava; Moreno, Vanessa; Balark, Shawn; Smith, A.; Sonilal, Marilyn; Tejpal, Neelam; Buren, Charles T. Van

doi:10.1002/jcla.20459

Cited by 16 publications

(4 citation statements)

References 11 publications

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“…12 This strategy of quantifying EVL by "cheating" IAs developed for SRL is not new and has undergone in-depth investigations in the past, producing conflicting results on its reliability. [20][21][22][23][24][25] Indeed, under most favorable conditions (ie, calibration with EVL), comparison with EVL-specific IAs is characterized by a high linear correlation, proportional bias of 30% (ie, slope = 1.3), and lack of individual agreement. 25 Therefore, our findings agree with the effects of low specificity toward EVL that characterize the "cheating" assays, and this should raise awareness of the actual limits to the interchangeability of ACMIA/EVRO despite its excellent analytical performance.…”

Section: Discussionmentioning

confidence: 99%

Analytical Performance of the New Siemens Affinity Chrome-Mediated Immunoassay Everolimus Assay and Its Interchangeability With the Thermo Quantitative Microsphere System for Routine Therapeutic Drug Monitoring of Patients After Solid Organ Transplantation

Ialongo

Sapio

Angeloni

2023

Therapeutic Drug Monitoring

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Background: A new homogeneous affinity chrome-mediated immunoassay (ACMIA) "EVRO" from Siemens Healthcare was evaluated for therapeutic drug monitoring of everolimus (EVL) with automated sample pretreatment and compared with quantitative microsphere system (QMS) "EVER" from Thermo Fisher Scientific.Methods: Imprecision, inaccuracy, and limit of quantitation (LoQ) of ACMIA/EVRO were verified using both hemolysate quality control (QC) samples and pooled whole blood specimens. The interchangeability of methods and the agreement of results were analyzed using 72 specimens (from 38, 30, and 4 kidney, liver, and lung transplant recipients, respectively).Results: Within-run imprecision ranged within %CV = 2.81-2.53 with pooled whole blood specimens and within %CV = 2.88-2.53 with QCs; total imprecision with QCs was within %CV = 2.14-1.51. Inaccuracy with value assigned QC was %O = 5.36 at the 5.6 ng/ mL level and %O = 5.56 at the 11.7 ng/mL level. LoQ was 0.93 ng/mL (%CV = 10). Passing-Bablok regression showed a constant bias of 0.679 ng/mL (95% CI: 0.216-1.026) and a proportional bias of 1.326 (95% CI: 1.240-1.425). Bland-Altman analysis showed 5/ 72 (6.9%) paired differences exceeding the limits of agreement and 1/72 (1.4%) paired differences exceeding 1.96 SD to a combined bias of 39.9% after detrending.Conclusions: ACMIA/EVRO shows satisfactory analytical performances that comply with recommendations, but it does not fulfill requirements for interchangeability with QMS/EVER. Particularly, this new assay using sirolimus-specific antibody shows a sizable proportional bias versus the more specific comparator, which may be because of EVL metabolites. This is supported by the lack of agreement for individual differences in most samples collected at the peak concentration (C2). Therefore, further evidence is needed to support the transition of EVL level monitoring from QMS/EVER to ACMIA/EVRO without making extensive changes to both reference interval and patient's baseline.

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Section: Discussionmentioning

confidence: 99%

Analytical Performance of the New Siemens Affinity Chrome-Mediated Immunoassay Everolimus Assay and Its Interchangeability With the Thermo Quantitative Microsphere System for Routine Therapeutic Drug Monitoring of Patients After Solid Organ Transplantation

Ialongo

Sapio

Angeloni

2023

Therapeutic Drug Monitoring

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“…Adverse events were evaluated every cycle and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE 4.0, May 2009) ( 9 ). The plasma concentration of everolimus was determined by measuring the serum concentration of rapamycin and converted with the reported formula ( 10 ).…”

Section: Methodsmentioning

confidence: 99%

Everolimus in Invasive Malignant Renal Epithelioid Angiomyolipoma

Guo

Zhang

2021

Front. Oncol.

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BackgroundTo evaluate the efficacy and safety of everolimus, a mTOR inhibitor, on invasive malignant renal epithelioid angiomyolipoma (EAML).Materials and MethodsFrom Oct 2014 to May 2019, we collected data from seven patients with a definite (clinical and pathological) diagnosis of EAML received everolimus in our hospital. Targeted sequence capture array technique with next-generation of high throughput sequencing (NGS) were performed to detect mutations of TSC1/2 genes. All patients had received surgery and everolimus. The clinical efficacy and safety of the therapy were evaluated.ResultsMutations of TSC1 and TSC2 were detected in two and three patients though targeted sequence capture array technique with NGS, respectively. Among seven patients, three had missense mutations, one had nonsense mutation, and one had the large fragment deletion mutation. Five patients accompanied with tuberous sclerosis complex (TSC) were identified. All patients were administered 10mg everolimus once daily, the treatment duration lasted for 3 to 28 months. The objective response was assessed 3 months later, five partial response, two stable disease (SD), the mean greatest tumor diameter of all patients decreased from 9.6 to 5.2cm. Six patients stayed SD and one patient died during follow up. Patients accompanying with TSC had better responses to everolimus compared with non-TSC.ConclusionThe mTOR inhibitor can be an effective treatment for patients with invasive malignant renal EAML. Patients with TSC may benefit more from the therapy.

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“…CTCAE V4.0 standard was used for safety evaluation. Fasting serum of the patients before taking the drug in the morning was tested for serum trough concentration of rapamycin (x) with the immunological method, and then the serum trough concentration of everolimus (y) was obtained by formula conversion, the specific formula is y = 1.29x − 0.068 [ 5 ]. The primary study endpoint was a reduction of RAML volume by 50% or more relative to baseline.…”

Section: Methodsmentioning

confidence: 99%

Sequential everolimus for angiomyolipoma associated with tuberous sclerosis complex: a prospective cohort study

Peng

Zhang

et al. 2021

Orphanet J Rare Dis

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Background To evaluate the efficacy, safety and health economics of sequential everolimus in treating angiomyolipoma (AML) associated with tuberous sclerosis complex (TSC). Methods In this prospective cohort study, patients met the inclusion criteria received standard or sequential treatment according to their willingness. All patients received an initial dose of everolimus (10 mg oral, once a day) for 3 months. The standard treatment group maintained 10 mg QD for 12 months, while the sequential treatment group reduced the dose to 5 mg QD from the 4th month. The efficacy, serum everolimus concentration and safety were evaluated at 1, 3, 6, 9 and 12 months after treatment. The primary efficacy endpoint was the proportion of patients with confirmed angiomyolipoma response of at least a 50% reduction in the total volume of target AML relative to baseline. Results Between June 1, 2016 and June 1, 2017, a total of 53 patients were included. Twenty-three patients received standard treatment, 30 patients received sequential treatment. At 1, 3, 6, 9 and 12 months after treatment, the proportion of patients whose total target tumor volume decreased by ≥ 50% from baseline was 39.1% versus 36.7%, 43.5% versus 56.7%, 47.8% versus 50%, 47.8% versus 60% and 47.8% versus 23.3% respectively (P > 0.05 for all). The overall response rate of skin lesions in the two groups was 40.4%, and the response rates of skin lesions at different times were similar for two groups (P > 0.05 for all). Major adverse effects (AEs) included mouth ulceration, hypertriglyceridemia, hypercholesterolemia, menstrual disorders. There was no significant difference between the two groups in the incidence of AEs at 3 months after treatment. The incidence of overall and grade 3/4 AEs at 12 months after treatment were significantly lower in the sequential treatment group. The average direct cost of the two groups in 12 months was $15,466 and $11,120, respectively. Conclusions Compared to standard treatment, sequential treatment was equally effective, with a lower incidence of adverse events and a lower direct cost, suggesting that it may be an alternative treatment for AML associated with TSC.

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Rapid estimation of whole blood everolimus concentrations using architect sirolimus immunoassay and mathematical equations: comparison with everolimus values determined by liquid chromatography/mass spectrometry

Cited by 16 publications

References 11 publications

Analytical Performance of the New Siemens Affinity Chrome-Mediated Immunoassay Everolimus Assay and Its Interchangeability With the Thermo Quantitative Microsphere System for Routine Therapeutic Drug Monitoring of Patients After Solid Organ Transplantation

Analytical Performance of the New Siemens Affinity Chrome-Mediated Immunoassay Everolimus Assay and Its Interchangeability With the Thermo Quantitative Microsphere System for Routine Therapeutic Drug Monitoring of Patients After Solid Organ Transplantation

Everolimus in Invasive Malignant Renal Epithelioid Angiomyolipoma

Sequential everolimus for angiomyolipoma associated with tuberous sclerosis complex: a prospective cohort study

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