Daratumumab is a CD38-directed antibody increasingly used for the treatment of adult patients with multiple mieloma. The membrane of red blood cells express CD38 and thus samples from patients treated with daratumumab show agglutination in red blood cell antibody screen tests performed prior to transfusion. This interference hinders the detection of red blood cell alloantibodies. Published literature has described a method to eliminate CD38 in red blood cells with DTT (Chapuy, 2016). This technique is cumbersome, requires positive and negative controls as DTT destroys Kell antigens and can produce in vitro hemolysis. The increasing number of multiple myeloma patients treated with daratumumab poses the need for a simple and straightforward technique with applicability in standard transfusion centers. DaraEx (Inno-Train) is a new anti-CD38 neutralizing agent that overcomes daratumumab-induced interferences detected in pre-transfusion tests without the major drawbacks associated with the DTT technique.
Our aim was to validate and implement DaraEx as the method of choice to solve daratumumab interferences detected in pre-transfusion screen tests in a tertiary care center.
A two-step approach using in vitro and in vivo samples was designed to validate the new method. First, we compared DaraEx efficacy in vitro to the reference DTT method in two samples spiked with daratumumab to achieve a concentration of 10mg/mL (Sample A: serum from a patient without known red blood cell alloantibodies; Sample B: serum from a patient with alloantibody anti-c). Red blood cells in the screen test (3 red blood cell screen; ID-DiaCell I-II-III) as well as positive (E+ red blood cells) and negative controls (K+ red blood cells) were treated with DTT 0.2M solution for 30 minutes at 37ºC and then washed four times with saline. In parallel, red blood cells in the screen test were incubated during 30 minutes at room temperature in a shaker (600rpm) with DaraEx. Red blood cells treated with each of these methods were used for indirect antiglobulin test with our gel card system (BioRad; IH-1000). Preference of method in terms of time needed and result interpretation was evaluated by three hematologists specialized in blood banking and four different technicians. Secondly, we tested pre-transfusion samples from patients treated with daratumumab with the DaraEx technique to check in vivo efficacy.
There was a 100% concordance between both techniques (DDT reference method and DaraEx new method) in both in vitro samples. All hematologists and technicians found the DaraEx technique less cumbersome in terms of processing and time to result (2 hours with DTT versus 1 hour with DaraEx) and the interpretation straightforward.
Twelve samples with daratumumab-induced interference in pre-transfusion screen tests belonging to 5 patients were tested between January and July 2019. All the interferences detected resolved with DaraEx regardless of time from last daratumumab administration (range: 7-145 days; mean: 57 days). Figure 1 shows screen test with and without treatment with DaraEx in a patient sample.
In our experience, DaraEx technique is a simple, fast and efficacious method, regardless of time from last daratumumab administration, to resolve interferences secondary to daratumumab administration without the major disadvantages associated with DTT.
Figure 1
Disclosures
García Gutiérrez: Pfizer: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding.
Photoacoustic Flow Cytometry for Single Sickle Cell DetectionIn VitroandIn Vivo
