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.
STUDY DESIGN AND 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.
DISCUSSION: 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.