34 Daratumumab Interference With Serum Protein Electrophoresis

Daratumumab is a fully human anti-CD38 IgG1-κ monoclonal antibody (mAb) approved by the US Food and Drug Administration in 2016 for the treatment of relapsed or refractory plasma cell myeloma. Since its adoption, concerns have been raised about the possibility of interference with the results of serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE) assays, especially for IgG/κ myeloma cases. Although daratumumab-specific immunofixation electrophoresis reflex assay (DIRA) is being evaluated, it has not been implemented in most clinical laboratories. SPE and IFE data in patients treated with daratumumab are rarely reported. We evaluated SPE and IFE results on patients being treated by daratumumab and present a representative case. We found that daratumumab can be readily detected by both SPE and IFE in patients treated with a standard therapeutic dose using SPIFE 3000 (Helena Lab, Beaumont, TX). It migrates late in the γ zone and the trough level of weekly daratumumab corresponds to an IgG/κ M-protein band between 0.1 and 0.2 g/dL. In an example case, an 86-year-old woman with recurrent multiple plasmacytoma had no history of monoclonal proteins in her SPE and IFE in the past. In August 2016, she started weekly daratumumab therapy. On her next SPE and IFE, a monoclonal IgG/κ band appeared as an M-spike of 0.23 g/dL. With these results, her clinical diagnosis was changed to IgG/κ multiple myeloma. In conclusion, daratumumab can interfere with SPE and IFE interpretation in IgG/κ myeloma, as well as in any other monoclonal gammopathies. Before a better solution can be implemented, the laboratory should become familiar with the properties of daratumumab on SPE and IFE, and investigate the clinical history for therapeutic mAb use in suspicious cases to avoid misdiagnosis.