Review: Effects of anti‐CD38 monoclonal antibodies on red blood cell transfusion and interventions

Abstract

Highly expressed in almost all myeloma cells, CD38 is an attractive treatment target. Anti-CD38 monoclonal antibodies have been approved for first-line treatment in non-transplantable multiple myeloma (MM) patients. In the future, they are likely to be approved for more indications. However, it has been found in clinical use that anti-CD38 monoclonal antibodies bind to CD38 on red blood cells (RBCs) and cause pan agglutination in indirect antiglobulin test (IAT), resulting in false positives of IAT 1,2 and, thereby, interfering with blood bank testing and leading to the delay of further diagnosis and treatment. Due to the high incidence of bone marrow suppression and anemia after chemotherapy or during bone marrow transplantation, most myeloma patients will need to receive RBC transfusion.With more and more patients receiving anti-CD38 treatment, it is of great importance to recognize this problem and optimize relevant diagnosis and treatment procedures to prevent RBC transfusion delays and reduce laboratory costs. In this article, we will review the mechanisms and the interventions of the impact from anti-CD38 monoclonal antibodies on red blood cell transfusion. | MECHANIS MIn multiple domestic and foreign studies, it was found that, following treatment with anti-CD38 monoclonal antibodies for 2-6 months, IAT was falsely positive in patients, resulting in positive antibody screens and incompatible crossmatches. This phenomenon occurs

Monoclonal Antibodies: The Greatest Resource to Treat Multiple Myeloma

“…Dithiothreitol (DTT), proteolytic enzymes, and CD38-deficient RBCs from neonatal cord blood may be used, if possible, to process reagent RBC in the IAT; papain, excessive soluble CD38 protein, and anti-CD38 monoclonal antibodies may be used to interfere with anti-CD38 monoclonal antibodies in serum; and RBC antigen genotyping may be carried out before transfusion. DTT is currently the approach that is used the most [ 32 ].…”

Anti-CD38 Monoclonal Antibodies Interfere With Isoagglutinin Detection

“…Arnaud Del Bello, MD, PhD, 1,2 Nassim Kamar, MD, PhD, 1,2,3 Olivier Cointault, MD, 1 Guillaume Vieu, PharmD, 4 and Katia Gauthier, MD 4 A BO-incompatible (ABOi) kidney transplantation is considered a safe procedure, respecting preformed donor-specific isoagglutinin elimination before the surgery. 1 Hemagglutination remains the most frequently used method to detect isoagglutinin.…”

“…The binding of daratumumab on CD38 that is highly expressed on the surface of red blood cells and myeloma cells induces their agglutination, leading to a false-positive isoagglutination test until 2 to 6 months postadministration. 3 Dithiothreitol disrupts the bridging of the disulfide bonds between amino acid residues necessary for structural conformation of some proteins, such as the CD38 antigen (which presents 5 bridges). Hence, dithiothreitol prevents anti-CD38 binding on red blood cells treated and overcomes the interference of the daratumumab and agglutination tests.…”