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.
authors.forename: Christopher
authors.initials: C
authors.lastname: McCudden
authors.forename: Amy E
authors.initials: AE
authors.lastname: Axel
authors.forename: Dominique
authors.initials: D
authors.lastname: Slaets
authors.forename: Thomas
authors.initials: T
authors.lastname: Dejoie
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Clemens
authors.forename: Sandy
authors.initials: S
authors.lastname: Frans
authors.forename: Jaime
authors.initials: J
authors.lastname: Bald
authors.forename: Torben
authors.initials: T
authors.lastname: Plesner
authors.forename: Joannes F M
authors.initials: JF
authors.lastname: Jacobs
authors.forename: Niels W C J
authors.initials: NW
authors.lastname: van de Donk
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Schecter
authors.forename: Tahamtan
authors.initials: T
authors.lastname: Ahmadi
authors.forename: A Kate
authors.initials: AK
authors.lastname: Sasser
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001797:Blood Protein Electrophoresis; D003429:Cross Reactions; D003951:Diagnostic Errors / Q000517:prevention & control; D006801:Humans; D007122:Immunoelectrophoresis; D007074:Immunoglobulin G / Q000097:blood; D007145:Immunoglobulin kappa-Chains / Q000097:blood; D057230:Limit of Detection; D051379:Mice; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology; D009194:Myeloma Proteins / Q000032:analysis; D015203:Reproducibility of Results
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains; D009194:Myeloma Proteins; C556306:daratumumab