Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter January 21, 2016

Interference of daratumumab in monitoring multiple myeloma patients using serum immunofixation electrophoresis can be abrogated using the daratumumab IFE reflex assay (DIRA)

  • Niels W.C.J. van de Donk , Henny G. Otten , Omar El Haddad , Amy Axel , A. Kate Sasser , Sandra Croockewit and Joannes F.M. Jacobs EMAIL logo

Abstract

Daratumumab is a fully human anti-CD38 IgG1-κ monoclonal antibody (mAb) currently being evaluated in several Phase 2 and 3 clinical studies for the treatment of multiple myeloma (MM). In this clinical case study we demonstrate that daratumumab can be detected as an individual monoclonal band in serum immunofixation electrophoresis (IFE). M-protein follow-up by IFE is part of the International Myeloma Working Group (IMWG) criteria to assess treatment response. Therefore, it is crucial that the daratumumab band is not confused with the endogenous M-protein of the patient during IFE interpretation. Moreover, a significant number of IgG-κ M-proteins co-migrate with daratumumab. Co-migration introduces a bias in the M-protein quantification since pharmacokinetic studies show that daratumumab peak plasma concentrations reach up to 1 g/L. More importantly, co-migration can mask clearance of the M-protein by IFE which is necessary for classification of complete response by IMWG criteria (negative serum IFE). For optimal M-protein monitoring the laboratory specialist needs to be informed when patients receive daratumumab, and it is essential that the laboratory specialist is aware that a slow migrating band in the γ-region in those patients may be derived from the daratumumab. A daratumumab specific IFE reflex assay (DIRA) has been developed and can be utilized to abrogate interference. The here described mAb interference is not limited to daratumumab, and as therapeutic antibodies gain approval and enter into common clinical practice, laboratory specialists will need additional processes to characterize IFE interference and distinguish endogenous M-protein from therapeutic antibodies.


Corresponding author: Joannes F.M. Jacobs, PhD, MD, Department of Laboratory Medicine; Radboud university medical center, Laboratory Medical Immunology (route 469), Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands, Phone: +31 (0)24-3617414, Fax: +31 (0)24-3619415

References

1. Maleki LA, Baradaran B, Majidi J, Mohammadian M, Shahneh FZ. Future prospects of monoclonal antibodies as magic bullets in immunotherapy. Human Antibodies 2013;22:9–13.10.3233/HAB-130266Search in Google Scholar PubMed

2. Ruinemans-Koerts J, Verkroost C, Schmidt-Hieltjes Y, Wiegers C, Curvers J, Thelen M, et al. Interference of therapeutic monoclonal immunoglobulins in the investigation of M-proteins. Clin Chem Lab Med 2014;52:e235–7.10.1515/cclm-2013-0898Search in Google Scholar PubMed

3. McCudden CR, Voorhees PM, Hainsworth SA, Whinna HC, Chapman JF, Hammett-Stabler CA, et al. Interference of monoclonal antibody therapies with serum protein electrophoresis tests. Clin Chem 2010;56:1897–9.10.1373/clinchem.2010.152116Search in Google Scholar PubMed

4. de Weers M, Tai YT, van der Veer MS, Bakker JM, Vink T, Jacobs DC, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol 2011;186:1840–8.10.4049/jimmunol.1003032Search in Google Scholar PubMed

5. Laubach JP, Richardson PG. CD38-Targeted immunochemotherapy in refractory multiple myeloma: a New Horizon. Clin Cancer Res 2015;21:2660–2.10.1158/1078-0432.CCR-14-3190Search in Google Scholar PubMed

6. Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med 2015;373:1207–19.10.1056/NEJMoa1506348Search in Google Scholar PubMed

7. Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K, et al. International uniform response criteria for multiple myeloma. Leukemia 2006;20:1467–73.10.1038/sj.leu.2404284Search in Google Scholar PubMed

8. Ludwig H, Miguel JS, Dimopoulos MA, Palumbo A, Garcia Sanz R, Powles R, et al. International Myeloma Working Group recommendations for global myeloma care. Leukemia 2014;28:981–92.10.1038/leu.2013.293Search in Google Scholar PubMed

9. Schmitz MF, Otten HG, Franssen LE, van Dorp S, Strooisma T, Lokhorst HM, et al. Secondary monoclonal gammopathy of undetermined significance after allogeneic stem cell transplantation in multiple myeloma. Haematologica 2014;99:1846–53.10.3324/haematol.2014.111104Search in Google Scholar PubMed PubMed Central

10. McCudden C, Axel AE, Slaets D, Dejoie T, Clemens PL, Frans S, et al. Monitoring multiple myeloma patients treated with daratumumab: teasing out monoclonal antibody interference. Clin Chem Lab Med 2016;54:1095–104.10.1515/cclm-2015-1031Search in Google Scholar PubMed

11. Brioli A, Giles H, Pawlyn C, Campbell JP, Kaiser MF, Melchor L, et al. Serum free immunoglobulin light chain evaluation as a marker of impact from intraclonal heterogeneity on myeloma outcome. Blood 2014;123:3414–9.10.1182/blood-2013-12-542662Search in Google Scholar PubMed

12. Axel AE, McCudden CR, Xie H, Hall BM, Sasser AK. Development of clinical assay to mitigate daratumumab, an IgG1k monoclonal antibody, interference with serum immunofixation (IFE) and clinical assessment of M-protein response in multiple myeloma. Cancer Res 2014;74:abstract nr 2563.10.1158/1538-7445.AM2014-2563Search in Google Scholar

13. Jacobs JF, van der Molen RG, Keren DF. Relatively restricted migration of polyclonal IgG4 may mimic a monoclonal gammopathy in IgG4-related disease. Am J Clin Pathol 2014;142:76–81.10.1309/AJCP41XCVBHEQCELSearch in Google Scholar PubMed

Received: 2015-9-11
Accepted: 2015-12-3
Published Online: 2016-1-21
Published in Print: 2016-6-1

©2016 by De Gruyter

Downloaded on 28.3.2024 from https://www.degruyter.com/document/doi/10.1515/cclm-2015-0888/html
Scroll to top button