Daratumumab, also known as Darzalex, DARA, or Dara-T, is a new medication recently approved in the US by the FDA to treat multiple myeloma. Daratumumab is a novel monoclonal antibody that targets CD38, an integral membrane protein expressed on both plasma cells and red blood cells (RBC). So while the CD38 antibodies are busy destroying the malignant myelomatous plasma cells, they will also be binding onto RBCs. Thankfully, the anti-CD38 binding of RBCs has not been shown to cause severe hemolysis. However, it has been shown to result in false-positive screening test results in the blood bank in all media (saline, PEG, LISS).
The daratumumab effect manifests as a warm autoantibody and will pan-react to any testing carried out including indirect (IAT) and direct antiglobulin tests (DAT), antihuman globulin (AHG) testing, and antibody screening and identification panels. Thankfully, ABO/RhD testing is not affected. To summarize (adopted from AABB Bulletin #16-02):
- ABO/RhD typing: no issues.
- Immediate spin crossmatch: no issues.
- Antibody screen: all cells positive.
- Antibody identification panel: all cells positive (autocontrol may be positive or negative).
- DAT: positive or negative.
- AHG crossmatch: positive with all RBC units tested.
- Adsorptions: panreactivity cannot be eliminated.
Potential future techniques to resolve interference, such as anti-idiotype antibodies to neutralize anti-CD38 in vitro, are on the horizon. In the meantime however, our institution’s Blood Bank has asked the clinical teams and pharmacy to notify the Blood Bank if a patient is going to receive daratumumab so that a baseline type and screen and RBC antigen phenotype or genotype is performed prior to initiating treatment. Once the patient receives daratumumab dithiothreitol (DTT) is used to eliminate the CD38 antigen from the surface of the reagent RBCs thereby eliminating the antibody screen and panel panreactivity. DTT treatment also destroys antigens in the Kell family. Therefore, unless the patient is known to be Kell-positive by phenotype/genotype, Kell-negative units are provided to patients on daratumumab.
Communication between clinicians, pharmacy and Blood Bank when a patient is receiving daratumumab is paramount to prevent delays in Blood Bank testing and transfusion needs. Protocols to handle Blood Bank specimens from patients receiving daratumumab can help streamline testing and reduce turnaround time for transfusion.
For further reading check out the AABB Bulletin #16-02 issued this year.
-Thomas S. Rogers, DO is a third-year resident at the University of Vermont Medical Center, a clinical instructor at the University of Vermont College of Medicine, and the assistant medical director of the Blood Bank and Transfusion Medicine service.