Background/Case Studies: Monoclonal antibody therapeutic drugs such as Darzalex/Daratumumab are directed against specific transmembrane proteins (CD38) in patients with multiple myeloma and non-Hodgkin lymphoma. The anti-CD38 antibodies are known to interfere in the indirect antiglobulin test (IAT), making identification of the presence of any underlying allo antibodies difficult. The standard technique used in Immunohematology reference lab (IRL) is treatment of reagent red cells with 0.2M Dithiothreitol (DTT) which counteracts the anti-CD38 interference, but does come with drawbacks like destruction of KEL antigens or hemolysis. Another method of removing the anti-CD38 serologic interference is the imusyn DaraEx (For Research Use Only) neutralizing agent, which inhibits the agglutination effect of the anti-CD38 antibodies Daratumumab, Felzartamab, and Isatuximab in the IAT, and does not cause any red cell antigen destruction.
Study
Design/Methods: Ten previously identified anti-CD38 patients referred to the IRL for antibody consultation were tested in parallel with the current procedure of DTT treatment of the red cells and with the new DaraEx neutralizing reagent. DTT treated cells were tested using tube methodology and LISS enhancement, while DaraEx was directly added to the wells of GEL cards and tested using the ORTHO MTS workstation methodology. Effectiveness of the reagent to remove anti-CD38 interference and time comparison studies were analyzed during the validation.
Results/Findings: Both DTT treatment and DaraEx neutralizing reagent were successful at removing anti-CD38 interference, allowing alloantibodies to be excluded. KEL system antigens were not able to be excluded using DTT. All commonly encountered alloantibodies were able to be excluded using the DaraEx neutralizing agent, see Figure A. Overall, chemical treatment of DTT versus DaraEx neutralization was more than doubled, with an average of 100 minutes for DTT technique versus 46 minutes for DaraEx technique. Conclusions: Both methods, 0.2M DTT and DaraEx, proved to be effective at removing the anti-CD38 serologic interference. DaraEx appears to be the more favorable option in situations when a patient phenotypes cellano or Kpb negative, or when using the Gel column technique to accommodate smaller sample volumes. Taking cost into consideration, the use of DaraEx over 0.2M DTT treatment as the primary method, to routinely remove the anti-CD38 interference in the IRL may not be feasible.
