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3567 International Validation of a Dithiothreitol (DTT)-Based Method to Resolve the Daratumumab Interference with Blood Compatibility Testing

Basic Science and Clinical Practice in Blood Transfusion
Program: Oral and Poster Abstracts
Session: 401. Basic Science and Clinical Practice in Blood Transfusion: Poster III
Monday, December 7, 2015, 6:00 PM-8:00 PM
Hall A, Level 2 (Orange County Convention Center)

Claudia I Chapuy, MD1*, Maria D Aguad, MT(ASCP)2*, Rachel T Nicholson, MLS(ASCP)CM3*, James P AuBuchon, MD4*, Claudia S Cohn, MD, PhD5*, Meghan Delaney, DO, MPH6*, Joan Cid, MD, PhD7*, Walter Dzik, MD8, Mark K. Fung, MD, PhD9*, Andreas Greinacher, MD10, Ai Leen Ang, MD11*, Dana V. Devine, PhD12, Nancy M Dunbar, MD13*, Henk Garritsen, MD14*, Lawrence T Goodnough, MD15, Ross Herron, MD16*, Tor A. Hervig, MD, PhD17*, C. Michael Knudson, MD, PhD18*, Jose M Kutner, MD, PhD19, Frank Nizzi, DO20*, Suchitra Pandey, MD21*, Benjamin Rioux-Masse, MD, FRCPC22, Kathleen Selleng, MD10*, Joseph Sweeney, MD23*, Minoko Takanashi, MD, Ph.D24*, Aaron A.R. Tobian, MD, PhD25*, Lorna Wall, MSc26*, Silvano Wendel, MD, PhD27*, David A Westerman28, Meredith Unger, PhD, MBA29*, Parul Doshi30*, Michael F. Murphy, MD, FRCP, FRCPath31, Larry J. Dumont, PhD, MBA32, Richard M. Kaufman, MD2 and The BEST Collaborative33*

1St. Elizabeth's Medical Center, Boston, MA
2Brigham and Women's Hospital, Boston, MA
3Massachusetts General Hospital, Boston, MA
4Bloodworks Northwest, Seattle, WA
5University of Minnesota, Minneapolis
6Bloodworks Northwest, Seattle Children's Hospital, University of Washington, Seattle, WA
7Hospital Clinic, Barcelona, Spain
8Blood Transfuson Service, Massachusetts General Hospital, Boston, MA
9University of Vermont Medical Center, Burlington, VT
10Institute for Immunology & Transfusion Medicine, Ernst Moritz Arndt University, Greifswald, Germany
11Blood Services Group, Health Sciences Authority, Singapore, Singapore
12Univ. of British Columbia, Canadian Blood Services, Vancouver, BC, Canada
13Dartmouth Hitchcock Medical Center, Lebanon, NH
14Städtisches Klinikum Braunschweig gGmbH, Braunschweig, Germany
15Pathology and Medicine, Stanford University, Stanford, CA
16American Red Cross Blood Services, Pomona, CA
17Haukeland universitetssjukehus, Bergen, Norway
18University of Iowa Hospitals and Clinics, Iowa City, IA
19Hemotherapy and Cell Therapy Department, Hospital Israelita Albert Einstein, Sao Paulo, Brazil
20Blood Systems, Scottsdale, AZ
21Blood Centers of the Pacific, San Francisco, CA
22Department of Hematology and Transfusion Medicine, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada
23Blood Bank The Miriam Hospital, Barrington, RI
24Blood Service Headquarters, Japanese Red Cross, Tokyo, Japan
25John Hopkins Hospital, Baltimore
26New Zealand Blood Service, Auckland, New Zealand
27Hospital Sirio Libanes, Sao Paulo, Brazil
28Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, Australia
29Janssen, Inc., Raritan, NJ
30Janssen Research & Development, LLC, Spring House, PA
31NHS Blood and Transplant, Oxford, United Kingdom
32Dartmouth-Hitchcock Medical Center, Lebanon, NH
33Dartmouth-Hitchcock Medical Center, Hanover, NH

Introduction

Daratumumab (DARA), an IgG1k human monoclonal antibody (Ab) against CD38, is a promising novel therapy for multiple myeloma. However, direct binding of DARA to endogenous CD38 on reagent red blood cells (RBCs) interferes with routine blood bank serologic testing. We recently showed that treating reagent RBCs with DTT eliminates the DARA interference by denaturing cell surface CD38, allowing the safe transfusion of patients on DARA.1 This multicenter international study was aimed at validating the DTT method for use by blood banks worldwide.

Methods                                                                                              

Participating blood banks received two plasma sample unknowns. Sample 1 was spiked with DARA alone (5 mcg/mL). Sample 2 was spiked with DARA plus a clinically significant RBC Ab (anti-D (Rh immune globulin) or monoclonal anti-Fya or anti-s). Sites were instructed to first perform an Ab screen using their usual method (tube, gel, or solid phase), then to repeat the Ab screen using DTT-treated RBCs (gel or tube). If the Ab screen remained positive with DTT-treated RBCs (Sample 2), sites were to identify the unknown Ab using a DTT-treated RBC panel (gel or tube.) The primary outcome measure was the proportion of sites able to successfully identify the unknown Ab in the presence of DARA. Qualitative data were collected by online survey.

Results

Paired plasma sample unknowns were shipped to 25 study sites in North America, South America, Europe, Asia, and Australia/New Zealand. Data were received from 23 sites to date (Table). For the initial Ab screen, 10 sites used tube testing, 7 sites used gel, and 6 sites used solid phase. All sites observed DARA interference with the Ab screen (false positive agglutination reactions). All sites reported no DARA interference using DTT-treated RBCs. For Ab identification (Sample 2), 13 sites used tube testing and 10 sites used gel. 23/23 sites (100%) were able to correctly identify the unknown Ab using the DTT method. The Abs identified were: anti-Fya (9/9), anti-s (8/8), and anti-D (6/6). Feedback on the DTT method was mainly positive, with 86% of sites that responded to the survey indicating that they planned to use the DTT method to manage clinical samples from DARA-treated patients.

Conclusion

DARA consistently interferes with all three Ab screening methods currently used by blood banks (tube, gel, and solid phase.) Using DTT-treated RBCs, 23/23 (100%) of blood bank laboratories from around the world were able to identify a clinically significant Ab initially masked by the presence of DARA. The DTT method is robust, reproducible, and can be implemented by blood banks globally to help provide safe blood products to patients on DARA. As DTT denatures Kell antigens, K- RBC units should be provided when using the DTT method.

1.     Chapuy CI, Nicholson RT, Aguad MD, et al. Resolving the daratumumab interference with blood compatibility testing. Transfusion. 2015;55(6pt2):1545-1554.

Disclosures: Unger: Janssen: Employment . Doshi: Janssen: Employment . Kaufman: Janssen: Consultancy , Research Funding .

*signifies non-member of ASH