International validation of a dithiothreitol (DTT)-based method to resolve the daratumumab interference with blood compatibility testing.
Daratumumab (DARA) consistently interferes with routine blood bank serologic testing by directly binding to CD38 expressed on reagent red blood cells (RBCs). Treating RBCs with dithiothreitol (DTT) eliminates the DARA interference. We conducted an international, multicenter, blinded study aimed at validating the DTT method for use by blood bank laboratories worldwide.



Paired plasma sample unknowns were sent to 25 participating blood bank laboratories. Sample 1 was spiked with DARA only (10 µg/mL), and Sample 2 with DARA plus a clinically significant RBC antibody (anti-D [n = 6], anti-Fya[n = 9], or anti-s [n = 10]). Sites were instructed to perform an antibody screen with and without DTT-treated RBCs and to use a DTT-treated RBC panel for antibody identification. Qualitative data about the DTT method were collected by online survey. The primary outcome was the proportion of study sites able to identify the antibody unknown in the presence of DARA.



All sites observed the DARA interference with the antibody screen. The DARA interference was seen with all testing methods (gel, tube, or solid phase). Using the DTT method, 25 of 25 sites (100%) successfully identified the antibody unknown in the presence of DARA. Feedback on the DTT method was positive, with 17 of 19 (90%) sites responding to the survey indicating that they planned to use the DTT method to test clinical samples from DARA-treated patients.



The DTT method is robust and reproducible and can be implemented by transfusion services worldwide to help provide safe blood products to patients treated with DARA.
Dana-Farber Cancer Institute at St Elizabeth's Medical Center, Boston, Massachusetts.
Claudia I
CI
Chapuy
Brigham and Women's Hospital, Boston, Massachusetts.
Maria D
MD
Aguad
Massachusetts General Hospital, Boston, Massachusetts.
Rachel T
RT
Nicholson
Bloodworks Northwest, Seattle, Washington.
James P
0000-0002-7976-6871
JP
AuBuchon
University of Minnesota, Minneapolis, Minnesota.
Claudia S
CS
Cohn
Bloodworks Northwest, Seattle Children's Hospital, University of Washington, Seattle, Washington.
Meghan
M
Delaney
University of Vermont Medical Center, Burlington, Vermont.
Mark K
MK
Fung
Janssen, Inc, Raritan, New Jersey.
Meredith
M
Unger
Janssen Research & Development, Springhouse, Pennsylvania.
Parul
P
Doshi
NHS Blood and Transplant, Oxford, United Kingdom.
Michael F
MF
Murphy
Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.|Dartmouth-Hitchcock Medical Center, Hanover, New Hampshire.
Larry J
LJ
Dumont
Brigham and Women's Hospital, Boston, Massachusetts.
Richard M
RM
Kaufman
D000906:Antibodies / Q000032:analysis / Q000097:blood; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001771:Blood Banks / Q000592:standards; D058731:Blood Safety; D004229:Dithiothreitol / Q000494:pharmacology*; D006650:Histocompatibility Testing / Q000592:standards*; D006801:Humans; D008722:Methods; D011786:Quality Control; D016037:Single-Blind Method; D000094902:Blood Banking / Q000379:methods
D000906:Antibodies; D000911:Antibodies, Monoclonal; C556306:daratumumab; D004229:Dithiothreitol