Use of an in-house trypsin-based method to resolve the interference of daratumumab

Transfusion. 2021 Oct;61(10):3000-3007. doi: 10.1111/trf.16635. Epub 2021 Sep 1.

Abstract

Background: Daratumumab (DARA) is a monoclonal antibody for treatment of plasma cell myeloma targeting CD38, a surface molecule expressed on plasma cells and red blood cells (RBCs). This complicates blood bank testing, requiring dithiothreitol (DTT) to remove DARA interference. A simple in-house method of removing DARA interference without use of DTT, a potentially hazardous chemical, is desirable. We demonstrate a trypsin-based method to remove interference in antibody testing at a medical center (MC), with parallel testing at an immunohematology reference laboratory (IRL).

Study design and methods: Pre-DARA type and screen (T&S) samples were obtained from 61 patients for antibody testing and RBC phenotyping using untreated reagent RBCs. Subsequent post-DARA T&S testing was performed with untreated reagent RBCs to demonstrate interference and repeated after trypsin treatment. Positive trypsin-treated antibody screens were reflexed to antibody identification using trypsin-treated panel cells. Parallel testing was performed on the same post-DARA samples at IRL.

Results: DARA interference was detected in 61/61 (100%) samples by MC and IRL. After trypsin treatment, DARA interference was eliminated in 60/61 (98.4%) antibody screens by both institutions with an overall percent agreement of 96.7% (95% confidence interval [CI] 88.7%-99.6%). Identification of known alloantibodies was confirmed in 3/3 patients with 100% concordant results between MC and IRL. There were no false-negative results demonstrated by IRL's functionally CD38-negative controls.

Conclusion: Our in-house trypsin-based method enables pretransfusion testing of patients receiving DARA in an accurate and cost-effective manner without missing clinically significant alloantibodies. This presents an additional testing option where DTT use is undesirable.

Keywords: DTT; daratumumab; dithiothreitol; interference; trypsin.

MeSH terms

  • ADP-ribosyl Cyclase 1 / immunology
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / immunology
  • Antineoplastic Agents / therapeutic use*
  • Erythrocytes / drug effects
  • Erythrocytes / immunology
  • Humans
  • Immunologic Tests
  • Indicators and Reagents
  • Isoantibodies / immunology
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / immunology

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Indicators and Reagents
  • Isoantibodies
  • daratumumab
  • ADP-ribosyl Cyclase 1