Guidance for transfusion management in patients receiving magrolimab therapy (anti-CD47 monoclonal antibody).

Magrolimab (Hu5F9-G4) is a first-in-class anti-CD47 IgG4 monoclonal antibody, with potential applications in several malignancies including myelodysplastic syndrome. CD47 blockade in malignancy has been shown to promote antitumour effects. However, the ubiquity of CD47 on red blood cells can result in interference in pretransfusion immunohaematology investigations and hinder timely provision of red blood cell units, with potential to mask clinically significant alloantibodies. We reviewed the literature for pretransfusion interference seen with magrolimab and methods to circumvent potential issues, and sought to provide clinical and laboratory recommendations for safe local transfusion practices. These recommendations are based on expert opinion and available literature, including the Victorian Senior Transfusion Scientist working group and professional societies and organisations (Australian & New Zealand Society of Blood Transfusion and Lifeblood representatives), to establish consensus recommendations. Interference in the ABO group and antibody screen can occur, and baseline immunohaematology testing prior to magrolimab therapy is critical. Antibody screening using an antihuman globulin reagent that does not detect human IgG4 subclass may distinguish magrolimab interference from an underlying alloantibody in patient plasma. Clear and consistent protocols for laboratories and close communication with clinicians are paramount to facilitate timely and safe transfusion support for patients receiving magrolimab therapy. As local transfusion laboratories gain experience with magrolimab, this will assist in our understanding and comfort in managing these patients.

Considerations for pre-transfusion immunohaematology testing in patients receiving the anti-CD38 monoclonal antibody daratumumab for the treatment of multiple myeloma.

In recent years, the anti-CD38 monoclonal antibody daratumumab (Darzalex; Janssen-Cilag Pty Ltd) has been shown to be highly efficacious in relapsed and refractory multiple myeloma, with the final results of treatment in newly diagnosed patients awaited. Despite awareness of the potential interference of daratumumab in pre-transfusion immunohaematology testing during phase I and II clinical studies, there was a degree of unpreparedness in the community upon the introduction of this drug into the clinics, particularly the impact that it has on the operational processes in hospital transfusion laboratories and timely issue of red blood cells (RBCs). Anti-CD38 interference in pre-transfusion immunohaematology tests is a particular problem in patients being treated with daratumumab for multiple myeloma as many will require RBC transfusions during their disease treatment. Panagglutination caused by anti-CD38 monoclonal antibody during the indirect antiglobulin test may mask the presence of a clinically significant RBC alloantibody in the patient's plasma during the antibody screen and identification process, which may be overlooked, particularly in urgent situations, subsequently resulting in a delayed or acute haemolytic transfusion reaction. Here, we summarise daratumumab's effects on pre-transfusion immunohaematology testing and its impact on clinical practice and make practical recommendations based on a consensus from medical and scientific transfusion experts and myeloma specialists on behalf of the Australian and New Zealand Society of Blood Transfusion and Myeloma Scientific Advisory Group to Myeloma Australia, respectively.