Monitoring multiple myeloma patients treated with daratumumab: teasing out monoclonal antibody interference

Christopher McCudden, Amy E Axel, Dominique Slaets, Thomas Dejoie, Pamela L Clemens, Sandy Frans, Jaime Bald, Torben Plesner, Joannes F M Jacobs, Niels W C J van de Donk, Philippe Moreau, Jordan M Schecter, Tahamtan Ahmadi, A Kate Sasser

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

131 Downloads (Pure)

Resumé

BACKGROUND: Monoclonal antibodies are promising anti-myeloma treatments. As immunoglobulins, monoclonal antibodies have the potential to be identified by serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE). Therapeutic antibody interference with standard clinical SPE and IFE can confound the use of these tests for response assessment in clinical trials and disease monitoring.

METHODS: To discriminate between endogenous myeloma protein and daratumumab, a daratumumab-specific immunofixation electrophoresis reflex assay (DIRA) was developed using a mouse anti-daratumumab antibody. To evaluate whether anti-daratumumab bound to and shifted the migration pattern of daratumumab, it was spiked into daratumumab-containing serum and resolved by IFE/SPE. The presence (DIRA positive) or absence (DIRA negative) of residual M-protein in daratumumab-treated patient samples was evaluated using predetermined assessment criteria. DIRA was evaluated for specificity, limit of sensitivity, and reproducibility.

RESULTS: In all of the tested samples, DIRA distinguished between daratumumab and residual M-protein in commercial serum samples spiked with daratumumab and in daratumumab-treated patient samples. The DIRA limit of sensitivity was 0.2 g/L daratumumab, using spiking experiments. Results from DIRA were reproducible over multiple days, operators, and assays. The anti-daratumumab antibody was highly specific for daratumumab and did not shift endogenous M-protein.

CONCLUSIONS: As the treatment of myeloma evolves to incorporate novel monoclonal antibodies, additional solutions will be needed for clinical monitoring of patient responses to therapeutic regimens. In the interim, assays such as DIRA can inform clinical outcomes by distinguishing daratumumab from endogenous M-protein by IFE.

OriginalsprogEngelsk
TidsskriftClinical Chemistry and Laboratory Medicine
Vol/bind54
Udgave nummer6
Sider (fra-til)1095-104
ISSN1434-6621
DOI
StatusUdgivet - 1. jun. 2016

Fingeraftryk

Monoclonal Antibodies
Electrophoresis
Monitoring
Assays
daratumumab
Blood Proteins
Antibodies
Proteins
Myeloma Proteins
Physiologic Monitoring
Serum
Immunoglobulins

Citer dette

McCudden, C., Axel, A. E., Slaets, D., Dejoie, T., Clemens, P. L., Frans, S., ... Sasser, A. K. (2016). Monitoring multiple myeloma patients treated with daratumumab: teasing out monoclonal antibody interference. Clinical Chemistry and Laboratory Medicine, 54(6), 1095-104. https://doi.org/10.1515/cclm-2015-1031
McCudden, Christopher ; Axel, Amy E ; Slaets, Dominique ; Dejoie, Thomas ; Clemens, Pamela L ; Frans, Sandy ; Bald, Jaime ; Plesner, Torben ; Jacobs, Joannes F M ; van de Donk, Niels W C J ; Moreau, Philippe ; Schecter, Jordan M ; Ahmadi, Tahamtan ; Sasser, A Kate. / Monitoring multiple myeloma patients treated with daratumumab : teasing out monoclonal antibody interference. I: Clinical Chemistry and Laboratory Medicine. 2016 ; Bind 54, Nr. 6. s. 1095-104.
@article{8d68a4b30ec24e7c94a88000ccc87b92,
title = "Monitoring multiple myeloma patients treated with daratumumab: teasing out monoclonal antibody interference",
abstract = "BACKGROUND: Monoclonal antibodies are promising anti-myeloma treatments. As immunoglobulins, monoclonal antibodies have the potential to be identified by serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE). Therapeutic antibody interference with standard clinical SPE and IFE can confound the use of these tests for response assessment in clinical trials and disease monitoring.METHODS: To discriminate between endogenous myeloma protein and daratumumab, a daratumumab-specific immunofixation electrophoresis reflex assay (DIRA) was developed using a mouse anti-daratumumab antibody. To evaluate whether anti-daratumumab bound to and shifted the migration pattern of daratumumab, it was spiked into daratumumab-containing serum and resolved by IFE/SPE. The presence (DIRA positive) or absence (DIRA negative) of residual M-protein in daratumumab-treated patient samples was evaluated using predetermined assessment criteria. DIRA was evaluated for specificity, limit of sensitivity, and reproducibility.RESULTS: In all of the tested samples, DIRA distinguished between daratumumab and residual M-protein in commercial serum samples spiked with daratumumab and in daratumumab-treated patient samples. The DIRA limit of sensitivity was 0.2 g/L daratumumab, using spiking experiments. Results from DIRA were reproducible over multiple days, operators, and assays. The anti-daratumumab antibody was highly specific for daratumumab and did not shift endogenous M-protein.CONCLUSIONS: As the treatment of myeloma evolves to incorporate novel monoclonal antibodies, additional solutions will be needed for clinical monitoring of patient responses to therapeutic regimens. In the interim, assays such as DIRA can inform clinical outcomes by distinguishing daratumumab from endogenous M-protein by IFE.",
author = "Christopher McCudden and Axel, {Amy E} and Dominique Slaets and Thomas Dejoie and Clemens, {Pamela L} and Sandy Frans and Jaime Bald and Torben Plesner and Jacobs, {Joannes F M} and {van de Donk}, {Niels W C J} and Philippe Moreau and Schecter, {Jordan M} and Tahamtan Ahmadi and Sasser, {A Kate}",
year = "2016",
month = "6",
day = "1",
doi = "10.1515/cclm-2015-1031",
language = "English",
volume = "54",
pages = "1095--104",
journal = "Clinical Chemistry and Laboratory Medicine",
issn = "1434-6621",
publisher = "Walterde Gruyter GmbH",
number = "6",

}

McCudden, C, Axel, AE, Slaets, D, Dejoie, T, Clemens, PL, Frans, S, Bald, J, Plesner, T, Jacobs, JFM, van de Donk, NWCJ, Moreau, P, Schecter, JM, Ahmadi, T & Sasser, AK 2016, 'Monitoring multiple myeloma patients treated with daratumumab: teasing out monoclonal antibody interference', Clinical Chemistry and Laboratory Medicine, bind 54, nr. 6, s. 1095-104. https://doi.org/10.1515/cclm-2015-1031

Monitoring multiple myeloma patients treated with daratumumab : teasing out monoclonal antibody interference. / McCudden, Christopher; Axel, Amy E; Slaets, Dominique; Dejoie, Thomas; Clemens, Pamela L; Frans, Sandy; Bald, Jaime; Plesner, Torben; Jacobs, Joannes F M; van de Donk, Niels W C J; Moreau, Philippe; Schecter, Jordan M; Ahmadi, Tahamtan; Sasser, A Kate.

I: Clinical Chemistry and Laboratory Medicine, Bind 54, Nr. 6, 01.06.2016, s. 1095-104.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Monitoring multiple myeloma patients treated with daratumumab

T2 - teasing out monoclonal antibody interference

AU - McCudden, Christopher

AU - Axel, Amy E

AU - Slaets, Dominique

AU - Dejoie, Thomas

AU - Clemens, Pamela L

AU - Frans, Sandy

AU - Bald, Jaime

AU - Plesner, Torben

AU - Jacobs, Joannes F M

AU - van de Donk, Niels W C J

AU - Moreau, Philippe

AU - Schecter, Jordan M

AU - Ahmadi, Tahamtan

AU - Sasser, A Kate

PY - 2016/6/1

Y1 - 2016/6/1

N2 - BACKGROUND: Monoclonal antibodies are promising anti-myeloma treatments. As immunoglobulins, monoclonal antibodies have the potential to be identified by serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE). Therapeutic antibody interference with standard clinical SPE and IFE can confound the use of these tests for response assessment in clinical trials and disease monitoring.METHODS: To discriminate between endogenous myeloma protein and daratumumab, a daratumumab-specific immunofixation electrophoresis reflex assay (DIRA) was developed using a mouse anti-daratumumab antibody. To evaluate whether anti-daratumumab bound to and shifted the migration pattern of daratumumab, it was spiked into daratumumab-containing serum and resolved by IFE/SPE. The presence (DIRA positive) or absence (DIRA negative) of residual M-protein in daratumumab-treated patient samples was evaluated using predetermined assessment criteria. DIRA was evaluated for specificity, limit of sensitivity, and reproducibility.RESULTS: In all of the tested samples, DIRA distinguished between daratumumab and residual M-protein in commercial serum samples spiked with daratumumab and in daratumumab-treated patient samples. The DIRA limit of sensitivity was 0.2 g/L daratumumab, using spiking experiments. Results from DIRA were reproducible over multiple days, operators, and assays. The anti-daratumumab antibody was highly specific for daratumumab and did not shift endogenous M-protein.CONCLUSIONS: As the treatment of myeloma evolves to incorporate novel monoclonal antibodies, additional solutions will be needed for clinical monitoring of patient responses to therapeutic regimens. In the interim, assays such as DIRA can inform clinical outcomes by distinguishing daratumumab from endogenous M-protein by IFE.

AB - BACKGROUND: Monoclonal antibodies are promising anti-myeloma treatments. As immunoglobulins, monoclonal antibodies have the potential to be identified by serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE). Therapeutic antibody interference with standard clinical SPE and IFE can confound the use of these tests for response assessment in clinical trials and disease monitoring.METHODS: To discriminate between endogenous myeloma protein and daratumumab, a daratumumab-specific immunofixation electrophoresis reflex assay (DIRA) was developed using a mouse anti-daratumumab antibody. To evaluate whether anti-daratumumab bound to and shifted the migration pattern of daratumumab, it was spiked into daratumumab-containing serum and resolved by IFE/SPE. The presence (DIRA positive) or absence (DIRA negative) of residual M-protein in daratumumab-treated patient samples was evaluated using predetermined assessment criteria. DIRA was evaluated for specificity, limit of sensitivity, and reproducibility.RESULTS: In all of the tested samples, DIRA distinguished between daratumumab and residual M-protein in commercial serum samples spiked with daratumumab and in daratumumab-treated patient samples. The DIRA limit of sensitivity was 0.2 g/L daratumumab, using spiking experiments. Results from DIRA were reproducible over multiple days, operators, and assays. The anti-daratumumab antibody was highly specific for daratumumab and did not shift endogenous M-protein.CONCLUSIONS: As the treatment of myeloma evolves to incorporate novel monoclonal antibodies, additional solutions will be needed for clinical monitoring of patient responses to therapeutic regimens. In the interim, assays such as DIRA can inform clinical outcomes by distinguishing daratumumab from endogenous M-protein by IFE.

U2 - 10.1515/cclm-2015-1031

DO - 10.1515/cclm-2015-1031

M3 - Journal article

C2 - 27028734

VL - 54

SP - 1095

EP - 1104

JO - Clinical Chemistry and Laboratory Medicine

JF - Clinical Chemistry and Laboratory Medicine

SN - 1434-6621

IS - 6

ER -