Development of a Procedure to Resolve Daratumumab Interference in Pretransfusion Testing

Multiple myeloma is an incurable disease characterized by the proliferation of malignant plasma cells in the bone marrow. Daratumumab (DARA), a monoclonal antibody that targets the CD38 antigen expressed on malignant myeloma cells, has been approved as a promising new treatment for patients with this disease. Although it is an e ff ective medication, DARA presents challenges in transfusion medicine. Because normal red cells weakly express the CD38 antigen, panreactivity is observed during antibody-detection workups on patients treated with DARA; the panreactivity can mask the presence of any underlying alloantibodies. The American Association of Blood Banks (AABB) has issued a method on how to resolve DARA interference by managing reagent red cells with dithiothreitol (DTT), which cleaves the disul fi de bonds of the CD38 antigen. The primary objective of this study was to develop a protocol for resolving DARA interference in pretransfusion testing at the University of North Carolina Medical Center ’ s Transfusion Medicine Services based on the method described by the AABB. Optimal procedural conditions required 4 drops of DTT to 1 drop of packed phosphate-bu ff ered saline – washed reagent red cells incubated at 37 °C for 45 minutes. An antibody screen using untreated and DTT-treated reagent red cells with appropriate quality-control results indicated that DTT was successful at eliminating DARA-induced panreactivity. A cost analysis was performed to consider the expenses and time required for the implementation of an in-house procedure.