Antigen masking indirect antiglobulin test can mitigate the interference of Mezagitamab, a novel anti-CD38 antibody, in serological pre-transfusion testing.

OBJECTIVES

Investigation of the interference of mezagitamab in serological pre-transfusion testing and the use of DaraEx to overcome it.

BACKGROUND

Administration of anti-CD38 antibodies is a state-of-the-art therapy for patients diagnosed with multiple myeloma. However, treatment with the currently approved anti-CD38 antibodies regularly results in widespread agglutination of red blood cells in serological pre-transfusion testing, making the determination of irregular antibodies and timely transfusion of compatible blood a challenge. Mezagitamab, a novel monoclonal anti-CD38 antibody, is currently under clinical investigation, not only for the treatment of multiple myeloma but also for other indications such as generalised myasthenia gravis.

METHODS/MATERIALS: Mezagitamab or daratumumab spiked plasmas, with or without irregular antibodies, were tested in column agglutination technique cards. DaraEx was used to mitigate occurring interferences.

RESULTS

Mezagitamab interferes with the indirect antiglobulin test, with comparable titers but weaker reaction strengths than daratumumab. DaraEx, a reagent containing Fab fragments of an anti-CD38 antibody, is able to completely overcome this interference in the antigen masking indirect antiglobulin test (AMIAT). DaraEx treatment does not interfere with tested irregular antibodies.

CONCLUSION

All novel anti-CD38 antibodies, such as mezagitamab, have the potential to interfere in serological pre-transfusion testing. While masking only one epitope, DaraEx has so far been an effective mitigation for all clinical anti-CD38 antibodies.