Full immunohematological workup despite treatment with an anti-CD47 monoclonal antibody

Background

Magrolimab is a monoclonal antibody targeting CD47. As a checkpoint inhibitor, it blocks the "don't eat me" signal expressed by cancer cells to avoid macrophage mediated killing. As CD47 is highly expressed on the surface of red blood cells as well, this therapy interferes with immunohematological workup. MagroEx, a new diagnostic reagent, blocks this interference thus enabling full immunohematological workup despite treatment with Magrolimab.

Methods

Here, we present a case of a 74-year-old 80 kg male AML patient treated with a first course of Magrolimab in a clinical phase 3 study. Due to an expected need of packed red blood cells (pRBC), extended blood group typing and antibody screening were initiated prior to administration of study medication. Column agglutination technique (Bio-Rad) was utilized for standard serological testing as well as antibody screening and differentiation. During saturation with study medication, extended RBC antigen typing (Kell, Cellano) was performed in LISS/Coombs in addition to cold antibody (IgM) screening in saline.

Results

In indirect agglutination testing (IAT) utilizing standard MagroEx concentration no agglutination was observed in samples with low study medication titers. After maximum saturation with study medication, an alternative protocol employing higher MagroEx concentrations was required in order to inhibit the agglutinating effect mediated by the therapeutic antibody. This use of a larger amount of MagroEx resulted in complete inhibition of Magrolimab interference, even at maximal anti-CD47 levels. Thus, the exclusion of alloantibodies and the provision of compatible pRBC became possible. Subsequently the patient could be safely transfused even during Magrolimab therapy.

Conclusion

The anti-CD47 study medication impaired antibody screening as well as serological crossmatch right from the start of treatment. By applying MagroEx a reliable inhibition of Magrolimab was achieved, so that valid serological crossmatches and antibody screenings became possible. Prior to treatment, extended blood grouping and antibody screening should be initiated as early as possible, to maximize transfusion safety. Fortunately, AB0 blood group typing is possible until day 12 of treatment.

Offenlegung Interessenkonflikt:

R. B. is a shareholder of imusyn