Role of dithiothreitol in the resolution of pretransfusion immunohematology testing in patients receiving the anti-CD38 monoclonal antibody daratumumab for the treatment of multiple myeloma

Abstract

Abstract: INTRODUCTION: Daratumumab (Darzalex; Janssen-Cilag Pty Ltd), an anti-CD38 monoclonal antibody (MoAb), has demonstrated high efficacy in treating relapsed and refractory multiple myeloma (MM). It stands as the pioneering anti-CD38 MoAb approved by the US FDA (2015) and TGA Australia (2017). While targeting CD38 on myeloma cells, daratumumab poses a challenge in pretransfusion testing by inducing panreactivity in indirect antiglobulin tests (IATs) due to CD38 expression on red cells. This study investigates the role of dithiothreitol (DTT) in resolving pretransfusion immunohematology testing in patients treated with daratumumab for MM. MATERIALS AND METHODS: Pretransfusion samples from three hematological patients diagnosed with MM and receiving anti-CD38 drugs necessitating red cell transfusion were subjected to immunohematology serological testing. Clinicians provided patient information, including gender, age, transfusion history, and time between anti-CD38 MoAb infusion and sample collection. Tests included ABO/RhD typing, IAT, both polyspecific and monospecific direct antiglobulin test (DAT), antibody (Ab) screening, Ab identification, eluate preparation, and red cell crossmatch. Control tests were conducted by incubating patient samples at 37°C for 1 h. RESULTS: ABO/RhD typing remained unaffected, yet all samples exhibited panreactivity in IATs. Two samples showed positive DAT results but negative eluates. Treatment of reagent red blood cells (RBCs) with 0.2 M DTT effectively mitigated interference by anti-CD38 monoclonal antibodies, resulting in compatible red cell crossmatches. Notably, incubation of patient samples at 37°C for 1 h yielded identical results. CONCLUSION: Pretreatment of erythrocytes with DTT deactivated the CD38 antigen, eliminating reactivity with patient serum treated with daratumumab. DTT treatment of reagent RBCs emerges as an efficient and accessible strategy to counteract interference from anti-CD38 drugs in pretransfusion tests.