Journal article
International Validation of a Dithiothreitol (DTT)-Based Method to Resolve the Daratumumab Interference with Blood Compatibility Testing
Blood, Vol.126(23), pp.3567-3567
12/03/2015
DOI: 10.1182/blood.V126.23.3567.3567
Abstract
Abstract
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.
Details
- Title: Subtitle
- International Validation of a Dithiothreitol (DTT)-Based Method to Resolve the Daratumumab Interference with Blood Compatibility Testing
- Creators
- Claudia I Chapuy - St. Elizabeth's Medical CenterMaria D Aguad - Brigham and Women's HospitalRachel T Nicholson - Massachusetts General HospitalJames P AuBuchon - Bloodworks NorthwestClaudia S Cohn - University of Minnesota SystemMeghan Delaney - University of WashingtonJoan Cid - Hospital Clínic de BarcelonaWalter Dzik - Massachusetts General HospitalMark K. Fung - University of Vermont Medical CenterAndreas Greinacher - Greifswald University HospitalAi Leen Ang - Health Sciences AuthorityDana V. Devine - Canadian Blood ServicesNancy M Dunbar - Dartmouth–Hitchcock Medical CenterHenk Garritsen - Klinikum BraunschweigLawrence T Goodnough - Stanford UniversityRoss Herron - American Red CrossTor A. Hervig - Haukeland University HospitalC. Michael Knudson - University of IowaJose M Kutner - Hospital Israelita Albert EinsteinFrank Nizzi - VitalantSuchitra PandeyBenjamin Rioux-Masse - Centre Hospitalier de l’Université de MontréalKathleen Selleng - Greifswald University HospitalJoseph Sweeney - Miriam HospitalMinoko Takanashi - Japanese Red Cross Society, JapanAaron A.R. Tobian - Johns Hopkins HospitalLorna Wall - New Zealand Blood ServiceSilvano Wendel - Hospital Sírio-LibanêsDavid A Westerman - Peter MacCallum Cancer CentreMeredith Unger - JanssenParul Doshi - JanssenMichael F. Murphy - NHS Blood and TransplantLarry J. Dumont - Dartmouth–Hitchcock Medical CenterRichard M. Kaufman - Brigham and Women's HospitalBEST Collaborative (Institution)
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.126(23), pp.3567-3567
- DOI
- 10.1182/blood.V126.23.3567.3567
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 12/03/2015
- Academic Unit
- Pathology; Radiation Oncology
- Record Identifier
- 9984284547302771
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