Daratumumab Interference in Pretransfusion Testing Is Overcome by Addition of Daratumumab Fab Fragments to Patients’ Plasma
Open Access
- 12 March 2019
- journal article
- research article
- Published by S. Karger AG in Transfusion Medicine and Hemotherapy
- Vol. 46 (6), 423-430
- https://doi.org/10.1159/000495773
Abstract
Background: Daratumumab (DARA), an IgG1κ human monoclonal anti-CD38 antibody, is used for the treatment of refractory myeloma for example. Binding of DARA to CD38 on red blood cells (RBCs), however, leads to panagglutination in indirect antiglobulin testing and possibly masks clinically relevant alloantibodies. Dithiothreitol eliminates panreactivity by destroying CD38 but has the drawback of modifying certain blood group antigens and, thereby, impairs the detection of alloantibodies. Methods: DARA was digested for 16 h at 37°C using immobilized papain in a spin column, centrifuged, and washed, and the DARA-Fab fragments in pooled flow-throughs were stored at –20°C. DARA-Fab and test cells (ID-DiaCell I-II-III or ID-DiaPanel; BioRad) were incubated with human plasma spiked with DARA (plasma concentration up to 1,000 mg/L) or plasma from patients under DARA therapy at 37°C for 15 min. Thereafter, ID-Cards LISS/Coombs were used. Results: Immunofixation electrophoresis showed complete fragmentation of DARA into Fc and Fab fragments by papain proteolysis. DARA-Fab efficiently prevented RBC agglutination by patients’ plasma and by plasma spiked with DARA. Moreover, DARA-Fab did not interfere with the detection of alloantibodies. Conclusion: We present a quite easy, reproducible, and cost-effective method for DARA-Fab fragment preparation. Blocking CD38 epitopes with DARA-Fab easily overcomes DARA interference in pretransfusion testing without affecting alloantibody detection.Keywords
This publication has 17 references indexed in Scilit:
- Daratumumab (anti-CD38) induces loss of CD38 on red blood cellsBlood, 2017
- Response to: Interference of daratumumab on the serum protein electrophoresiscclm, 2017
- International validation of a dithiothreitol (DTT)‐based method to resolve the daratumumab interference with blood compatibility testingTransfusion, 2016
- Interference of New Drugs with Compatibility Testing for Blood TransfusionThe New England Journal of Medicine, 2016
- Positiver indirekter Antihumanglobulintest durch Daratumumab – Strategien für die transfusionsmedizinische VersorgungTransfusionsmedizin, 2016
- Targeting CD38 with Daratumumab Monotherapy in Multiple MyelomaThe New England Journal of Medicine, 2015
- When blood transfusion medicine becomes complicated due to interference by monoclonal antibody therapyTransfusion, 2015
- Resolving the daratumumab interference with blood compatibility testingTransfusion, 2015
- Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological TumorsThe Journal of Immunology, 2011
- CD38 Expression on CD8 T Lymphocytes as a Marker of Residual Virus Replication in Chronically HIV-Infected Patients Receiving Antiretroviral TherapyAIDS Research and Human Retroviruses, 2004