BACKGROUND: Daratumumab (DARA), a promising novel therapy for multiple myeloma, 
is an IgG1κ monoclonal antibody that recognizes CD38 on myeloma cells. During 
routine compatibility testing, we observed that the plasma of five of five 
DARA-treated patients demonstrated a positive antibody screen and panreactivity 
on red blood cell (RBC) panel testing. We hypothesized that the observed 
panreactivity reflected DARA binding to CD38 on reagent RBCs, and we 
investigated methods to prevent this binding.
STUDY DESIGN AND METHODS: DARA binding to CD38+ or CD38- HL60 cells was assessed 
by flow cytometry. To remove cell surface CD38, cells were incubated with 
dithiothreitol (DTT) or trypsin. Soluble CD38 or anti-DARA was used to 
neutralize DARA in solution. Routine blood bank serologic methods were used to 
test samples from DARA-treated patients and normal plasma samples spiked with 
DARA and/or alloantibodies.
RESULTS: Normal plasma samples spiked with DARA (0.1-10 µg/mL) and incubated 
with reagent RBCs recapitulated the interference observed with samples from 
DARA-treated patients. Flow cytometry experiments confirmed DARA binding to 
CD38+ HL60 cells, but not to CD38- controls. DTT treatment of CD38+ HL60 cells 
reduced DARA binding by 92% by denaturing cell surface CD38. Treating 
DARA-containing plasma with soluble CD38 or anti-DARA idiotype also inhibited 
DARA binding.
CONCLUSION: DARA causes panreactivity in vitro by binding to CD38 on reagent 
RBCs. Treating reagent RBCs with DTT is a robust method to negate the DARA 
interference, enabling the safe provision of blood to DARA-treated patients. 
Because DTT denatures Kell antigens, K- units are provided to these patients.