Daratumumab

One of two medications used for multiple myeloma treatment that is really just an antibody! Daratumumab (“DARA” for short) is simply a monoclonal antibody against a cell protein called “CD38.” CD38 is particularly abundant on the surface of plasma cells (the malignant cell in myeloma), and anti-CD38 has been clearly shown to damage and destroy malignant plasma cells in patients with myeloma. This is a very good and exciting thing, since multiple myeloma is a really, really difficult disease to treat! Anti-CD38 is now used as a primary treatment for myeloma in the US.

Unfortunately for those of us in blood bank world, CD38 is not only present on plasma cells, but is also found in smaller quantities on red blood cells. As a result, everyone who gets DARA also gets a built-in blood bank testing challenge (yay!). Since all reagent RBCs will carry CD38, patients who are taking anti-CD38 will have positive antibody screens, antibody identification panels with panagglutins that look kinda like warm autoantibodies, and incompatible AHG crossmatches (NOTE: ABO and Rh testing is not affected; only those tests that have an anti-human globulin phase are impacted).

In the blood bank, there are several strategies we can use to eliminate the anti-CD38 testing interference, including treating the reagent cells with DTT (dithiothreitol), which is a reagent that degrades CD38 on those reagent cells, making the incompatibility with the patient plasma go away in the testing environment. Unfortunately, this leads to other challenges. Since DTT also eliminates Kell system antigens, the patient should receive K- blood unless the patient is K+, since the DTT treatment of our screening RBCs makes us unable to detect antibodies against Kell system antigens. Matching these patients proactively is very important. I discussed this issue and others extensively in a Blood Bank Guy Essentials Podcast episode from May 2016.

Updated by Joe Chaffin, January 2024.

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