Canterbury DHB

Blood banking issues with Anti-CD38 and CD47 monoclonal antibodies

Certain monoclonal antibodies interfere with basic serological blood testing, due to the presence of their target antigens on the surface of RBCs. Currently daratumumab (Anti-CD38 antibody) is available on compassionate basis in New Zealand for treatment of relapsed/refractory myeloma. Anti-CD47 monoclonal antibodies are not yet FDA-approved but is being used in clinical trials in the treatment of solid organ and haematologic malignancies.

Anti-CD38 Antibodies (Daratumumab)

Daratumumab was FDA approved in 2015 as monotherapy or in combination for patients with relapsed/refractory myeloma. It targets CD38, which is an antigen present on plasma cells. Daratumumab is usually continued until disease progression. Its effects on serological testing in the blood bank continue for up to 6 months from last dose. CD38 is also expressed on many types of cells including B and T lymphocytes, NK cells and, most importantly from a blood-banking point of view, red blood cells (in low levels). Fetal red cells do not express CD38 and so do not react with daratumumab.

Effect on Serologic Testing

Daratumumab has no effect on forward or reverse grouping for ABO/Rh(D) as this is done with IgM at room temperature (daratumumab is IgG). Daratumumab binds to CD38 on RBCs and leads to a pan-reactive antibody screen (reaction strength usually weak but uniform). It also means that an IAT-crossmatch cannot be done as the daratumumab in the patient’s serum will react with the units cross-matched. Daratumumab cannot be adsorbed off RBC surfaces using standard laboratory techniques.

DAT (Direct Coombs test) is usually negative (unaffected by daratumumab).

Management

A pre-emptive approach is the best way of dealing with daratumumab.

If a patient is planned to have daratumumab:

• The current practice is to provide prophylactic antigen-matched (PAM) blood – matched for Rh, Kell, Duffy, Kidd, and S. This requires sending a sample to the blood bank for RBC phenotyping (or genotyping if transfused within 3 months – this takes place in Auckland reference lab) before starting the drug.
• Label the NZBS form clearly with “Pre-treatment with daratumumab – for RBC extended phenotyping/genotyping”.

If a patient has already received daratumumab:

• DTT-treated RBCs must be used to perform the antibody screen (and panel if needed). DTT eliminates CD38. It also eliminates some RBC antigens, most importantly Kell (Big K).
• Therefore, if an antibody panel against DTT-treated RBCs is negative, Kell-negative RBC units will need to be provided after that time. DTT-treatment of RBCs can only be done in reference laboratory in Auckland and will take at least 24 hours.

Anti-CD47 Antibodies

CD47 is part of the Rh system and is present on many cells, including RBCs (in high frequency) and platelets. Its presence leads to inhibition of APCs and protects the cell on which they are expressed from destruction/phagocytosis. CD47 is upregulated on certain haematologic and non-haematologic malignancies and is currently in phase II/III trials.

Anti-CD47 antibodies are associated with anaemia and thrombocytopenia.

Effect on Serologic Testing

Anti-CD47 antibodies interfere with reverse grouping (leading to “O” group appearance). It causes a pan-reactive antibody panel (strong reactions, 3-4+). DAT may be negative (false negative) or weakly positive but eluates are usually strongly pan-reactive. Cross-matching at IAT is not possible in the presence of Anti-CD47.

Management

Pre-emptive testing and extended phenotyping (or genotyping if recently transfused) should be done before starting Anti-CD4 testing.

Strategies to allow removal of Anti-CD47 are being explored. It is resistant to enzyme treatment.

Topic Code: 645246