New mAb therapies in multiple myeloma: interference with blood transfusion compatibility testing

Immunotherapeutic strategies are emerging as novel therapeutic approaches in multiple myeloma, with several mAbs being in advanced stages of clinical development. Of these, CD38 targeting antibodies appear very promising. In trials with anti-CD38 mAb daratumumab, all patients demonstrated panreactivity in red blood cell (RBC) panel testing, complicating the selection of compatible RBCs for transfusion. This review provides an overview of the interferences and solutions to safely transfuse these patients.

CD38 is weakly expressed on human erythrocytes. Since the first reports on the interference, different solutions have been reported, including the neutralization of anti-CD38 mAbs in plasma by sCD38 or antiidiotype antibodies, CD38 depletion of RBCs using dithiothreitol or cord blood test cells, and transfusion of extensively typed RBCs.

All methods have (dis)advantages, and it depends on the facilities of the immunohematology laboratory what strategy to choose. As the selection of suitable RBC units can be seriously delayed, hospitals should have protocols to communicate this interference with patients, laboratories, and physicians in a timely manner. As CD38 antibodies may also have a role in the treatment of diseases beyond hematological malignancies, chances are high that health professionals will encounter this issue in the nearby future.