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.