Multicenter evaluation of soluble CD38: neutralizing anti-CD38 pan-reactivity to enable alloantibody detection

Anti-CD38 is a monoclonal antibody treatment for multiple myeloma, B-cell malignancies, and autoimmune diseases that targets CD38 antigens on the cell surface. Red blood cells are CD38+, therefore anti-CD38 causes panagglutination, hindering immunohematology testing such as antibody screen, antibody identification, and crossmatch. This interference masks detection of clinically significant alloantibodies in pre-transfusion testing.

To assess the effectiveness of soluble CD38 (sCD38) in neutralizing anti-CD38 in the clinical setting and user satisfaction, plasma samples from patients receiving anti-CD38 therapy were collected between 0 and 150 days after the last infusion and tested according to routine laboratory procedures with an established sCD38 neutralization method (15 minutes incubation at 37°C with up to 6 μL of sCD38 per 25 μL of plasma). Neutralization was evaluated using antibody screening or crossmatching, by tube or gel card. Some samples were spiked with irregular antibodies to evaluate the impact of sCD38 on antibody detection. A survey assessed user satisfaction.

In total, 273 patient samples were evaluated (263 patients treated with daratumumab and 10 with isatuximab). sCD38 completely neutralized anti-CD38 present in 79.8% of samples tested using either 2 or 4 μL of sCD38. When either 2-4 or 6 μL of sCD38 was used, 98.5% of samples were neutralized. Except for anti-Fya and anti-Fyb, all spiked alloantibodies (anti-D, -c, -E, -K, -Jk^a, -Kp^a, -Lu^a, -S) were detected. The mean score for general satisfaction with sCD38 was 4.44 (with 5 [very satisfied] the highest score).

sCD38 has demonstrated strong potential in neutralizing anti-CD38 drugs in the clinical setting. While tested against isatuximab and daratumumab, it could be a potentially universal solution. By mimicking CD38 antigen on red blood cells, sCD38 is likely to interact with a broad range of anti-CD38 antibodies, suggesting its possible applicability across various settings.