title: When blood transfusion medicine becomes complicated due to interference by monoclonal antibody therapy.
abstract: BACKGROUND
  Monoclonal antibodies (MoAbs) are increasingly integrated in the standard of care. The notion that therapeutic MoAbs can interfere with clinical laboratory tests is an emerging concern that requires immediate recognition and the development of appropriate solutions. Here, we describe that treatment of multiple myeloma patients with daratumumab, a novel anti-CD38 MoAb, resulted in false-positive indirect antiglobulin tests (IATs) for all patients for 2 to 6 months after infusion. This precluded the correct identification of irregular blood group antibodies for patients requiring blood transfusion.
  
  
  METHODS
  The IAT was performed using three- and 11-donor-cell panels. Interference of daratumumab and three other anti-CD38 MoAbs was studied using fresh-frozen plasma spiked with different MoAb concentrations. Additionally it was tested whether two potentially neutralizing agents, anti-idiotype antibody and recombinant soluble CD38 (sCD38) extracellular domain, were able to inhibit the interference.
  
  
  RESULTS
  The CD38 MoAbs caused agglutination in the IAT in a dose-dependent manner. Addition of an excess of anti-idiotype antibodies or sCD38 protein to the test abrogated CD38 MoAb interference and successfully restored irregular antibody screening and identification.
  
  
  CONCLUSIONS
  CD38 MoAb therapy causes false-positive results in the IAT. The reliability of the test could be restored by adding a neutralizing agent against the CD38 MoAb to the patient's plasma. This study emphasizes that during drug development, targeted therapeutics should be investigated for potential interference with laboratory tests. Clinical laboratories should be informed when patients receive MoAb treatments and matched laboratory tests to prevent interference should be employed.
authors.affiliation: Department of Clinical Chemistry and Haematology, University Medical Center Utrecht.
authors.forename: Marlies
authors.initials: M
authors.lastname: Oostendorp
authors.affiliation: Genmab, Utrecht, The Netherlands.
authors.forename: Jeroen J
authors.initials: JJ
authors.lastname: Lammerts van Bueren
authors.affiliation: Janssen R&D LLC, Spring House (Ambler), Pennsylvania.
authors.forename: Parul
authors.initials: P
authors.lastname: Doshi
authors.affiliation: Janssen R&D LLC, Spring House (Ambler), Pennsylvania.
authors.forename: Imran
authors.initials: I
authors.lastname: Khan
authors.affiliation: Janssen R&D LLC, Spring House (Ambler), Pennsylvania.
authors.forename: Tahamtan
authors.initials: T
authors.lastname: Ahmadi
authors.affiliation: Genmab, Utrecht, The Netherlands.|Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Paul W H I
authors.initials: PW
authors.lastname: Parren
authors.affiliation: Department of Clinical Chemistry and Haematology, University Medical Center Utrecht.
authors.forename: Wouter W
authors.initials: WW
authors.lastname: van Solinge
authors.affiliation: Department of Clinical Chemistry and Haematology, University Medical Center Utrecht.
authors.forename: Karen M K
authors.initials: KM
authors.lastname: De Vooght
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000276:immunology* / Q000627:therapeutic use; D001788:Blood Grouping and Crossmatching / Q000592:standards; D001803:Blood Transfusion / Q000379:methods; D003298:Coombs Test / Q000592:standards; D003429:Cross Reactions; D005189:False Positive Reactions; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000276:immunology / Q000628:therapy; D012698:Serologic Tests
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C556306:daratumumab; D051997:ADP-ribosyl Cyclase 1