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.