PS1594 EXPERIENCE WITH THE NEUTRALIZING AGENT DARAEX® IN BLOOD COMPATIBILITY TESTS IN PATIENTS TREATED WITH DARATUMUMAB
Authors: Constantin E. Morente , Garcia P. Romero , Collado M.P. Garrido , Ruiz A. Garcia , Tamayo R. Rios , Chacón M. Jurado 
Published: June 2019

Background:

Daratumumab is a human monoclonal antibody used for the treatment of multiple myeloma, which binds to CD38, a protein that is expressed on red blood cells (RBCs). Therefore, the plasma of these patients reacts with the RBCs producing a panreactivity and interfering in the transfusion compatibility testing. Panagglutination may persist for up to 6 months after the last infusion of daratumumab. An anti‐CD38 antibody for treatment of multiple myeloma shows a strong interference in the indirect antiglobulin test (IAT) where most of the reactions turn to unspecifically (wrong) positive. The time consuming standard technique using Dithiothreitol (DTT) counteracts the interference but has major drawbacks like destruction of Kel antigens or hemolysis. The DaraEx® compound inhibits the agglutination effect of anti‐CD38 in IAT without side effects. DaraEx® is a neutralizing agent for the inhibition of the agglutination effect of the anti‐CD38 antibody daratumumab in IAT.

Aims:

To validate the procedure to resolve the interference of daratumumab in transfusion compatibility testing using red cells treated with DaraEx® for the inhibition of the agglutination effect of the anti‐CD38 antibody daratumumab in IAT. Daratumumab can interfere with crossmatching and antibody screening in the IAT, which will allow us to identify a clinically significant antibody that has been initially masked by the presence of daratumumab.

Methods:

The study has been conducted in 25 plasma samples of patients diagnosed with multiple myeloma who have been treated with daratumumab. Irregular antibody screening tests and CrossMatching were performed on all of them, being positive in all cases. We performed the technique to eliminate reactivity by treating the red cells used in compatibility tests with DaraEx®, which neutralizes CD38 on the surface of the erythrocyte, thereby preventing Daratumumab from binding and inducing agglutination. The material used was DaraEx®, 0.9% NaCl LISS/Coombs ID‐Cards and Test cell reagents for the ID‐System; We performed the method in Biovue Column Agglutination Technology and gel card systems.

Results:

After performing the technique, we were able to eliminate panreactivity in both Irregular antibody screening tests and CrossMatching.

Summary/Conclusion:

Daratumumab causes panreactivity in vitro by binding to CD38 on reagent RBCs. It is necessary to do a baseline antibody screen (type and screen) before starting the treatment with daratumumab. Treating reagent RBCs with DaraEx® is a useful easy and quick method to mitigate the interference created by antiCD38 mAbs in pretransfusion testing. DaraEx is a quick and simple procedure; it doesn’t affect other antigens or alloantibody reactions. It doesn’t have side effects like destruction of blood group antigens or hemolysis as described for the standard DTT treatment. Therefore, we consider it a very useful technique to resolve interferences produced by daratumumb with blood compatibility testing. We believe that it is essential to have a validated technique to resolve these discrepancies. If an emergency transfusion is required, noncrossmatched, ABO/RhD‐compatible RBCs can be given, per local blood bank practices.