Overcoming Drug Interference in Transfusion Testing: A Spotlight on Daratumumab

Abstract

Daratumumab, a monoclonal antibody therapeutic, is highly efficacious and widely used in all stages of multiple myeloma and amyloidosis and has promising activity in other hematologic disorders. Daratumumab interacts with red blood cells, interfering with pre-transfusion testing. This interference can lead to compromising transfusion safety, extensive blood bank work ups and delays in provision of compatible units. Several methods have been developed to negate daratumumab interference with indirect antiglobulin testing. They are based on i) standard blood bank techniques including dithiothreitol and enzymatic treatment of reagent cells, using reagent red blood cells negative for CD38, ii) blocking CD38 antigens on reagent or donor cells, iii) neutralization of anti-CD38 antibody in patient plasma prior to testing, and iv) extended antigen typing of patient red blood cells in conjunction with provision of phenotypically matched units for transfusion. Implementation of those methods by the blood bank should be a planned effort coordinated with the patient's clinical team. Timely involvement of blood bank and transfusion services and educational efforts by both blood banks and clinical providers can improve the overall daratumumab safety profile in regard to blood transfusion.

Roadmap for new practitioners to navigate the multiple myeloma landscape

“…To avoid significant delays in patient care, it is recommended to determine blood typing prior to first infusion [ 35 ]. If unobtainable, dithiothreitol (DTT) may be used to determine blood type post-daratumumab infusion [ 36 ].…”

Efficient neutralization of daratumumab in pretransfusion samples using a novel recombinant monoclonal anti‐idiotype antibody

“…Plasma samples from patients receiving anti‐CD38 consistently cause positive agglutination reactions in antibody detection tests (screens), antibody identification panels, and antihuman globulin cross matches, complicating pretransfusion testing and potentially delaying patient blood support. Several strategies have been employed to negate the anti‐CD38 interference, each with advantages and disadvantages 6 . The most common method is to treat reagent cells with 0.2 M dithiothreitol (DTT).…”

“…Several strategies have been employed to negate the anti-CD38 interference, each with advantages and disadvantages. 6 The most common method is to treat reagent cells with 0.2 M dithiothreitol (DTT). DTT denatures cell surface CD38, eliminating the anti-CD38 interference.…”

Interference Analysis of Monoclonal Antibody Cluster of Differentiation 38 on ABO Blood Group Identification and Cross-Matching

“…During the study of above projects, routine blood screening in blood banks showed consistently positive Indirect Anti-human globulin Test (IAT) results among patients who received daratumab therapy [9,10] . IAT, also called indirect Coombs test, typically used to test Red Blood Cell (RBC) alloantibody compatibility in plasma prior to transfusion [11,12] . Since CD38 is expressed on human erythrocytes, daratumumab may interfere with IAT by binding to endogenous CD38 present on the surface of RBC [12,13] .…”

“…IAT, also called indirect Coombs test, typically used to test Red Blood Cell (RBC) alloantibody compatibility in plasma prior to transfusion [11,12] . Since CD38 is expressed on human erythrocytes, daratumumab may interfere with IAT by binding to endogenous CD38 present on the surface of RBC [12,13] . In relapsed and refractory MM treatment, patients often have anemia and frequent need for blood transfusions, therefore, find and establish a blood group antibody screening and cross-matching program that excludes anti-CD38 monoclonal antibody interference has become an urgent problem to be solved in the blood transfusion department.…”