Daratumumab is CD38 monoclonal antibody that is effective in a variety of haematological malignancies, particularly multiple myeloma. The binding of the drug to CD38 cells induces immune mediated apoptosis through cross-linking to the Fc receptor. CD38 is primarily found on the surface of T cells, B cells, natural killer (NK) cells, neutrophils and myeloid cells, and it is also present in low volumes on red blood cells. The binding of Daratamumab to CD38 on the surface of red cells results in panagglutination (with resultant false reactive results) in the indirect antiglobulin test (IAT) used in antibody screening and crossmatch testing.
A commercial anti-sera, DaraEx, masks CD38 on the surface of red blood cells to prevent Daratumumab from binding and inducing agglutination. WCBS is currently investigating its use, although it is very expensive. An alternative to DaraEx is the treatment of red blood cells with dithiothreitol (DTT) that removes the drug from the cell surface. DTT counteracts the panagglutination but can denature or modify certain blood group antigens, in particular, Kell, Lutheran, YT, JMH, LW, Cromer, India, Dombrock and Knops systems, and prohibit binding of corresponding antibodies. For this reason, DTT is not used at WCBS.
In order to find suitably matched blood for these patients, our Immunohaematology Laboratory will screen the plasma for clinically significant antibodies, perform a direct antiglobulin test (DAT) using polyspecific anti-human globulin, and if necessary, monospecific anti-IgG and anti-C3d. An eluate is prepared from DAT reactive red cells in order to select suitably-matched blood for the patient. The procedure is time-consuming and we encourage clinicians to please send the crossmatch request, as far as possible, ahead of time.
For more information, please contact Ruwayda Soeker, Manager – Immunohaematology at 021 507 6339 or ruwayda@wcbs.org.za