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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

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Volume 54, Issue 6


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
  • Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Omar El Haddad
  • Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Amy Axel / A. Kate Sasser / Sandra Croockewit / Joannes F.M. Jacobs
  • Corresponding author
  • Department of Laboratory Medicine; Radboud university medical center, Laboratory Medical Immunology (route 469), Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2016-01-21 | DOI: https://doi.org/10.1515/cclm-2015-0888


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.

Keywords: daratumumab; daratumumab specific IFE reflex assay (DIRA); immunofixation electrophorsesis; monoclonal antibody; multiple myeloma; serum protein electrophoresis


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About the article

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

Received: 2015-09-11

Accepted: 2015-12-03

Published Online: 2016-01-21

Published in Print: 2016-06-01

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 54, Issue 6, Pages 1105–1109, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2015-0888.

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