Using Soluble CD38 to Overcome Daratumumab Interference in Pretransfusion Compatibility Testing

Background: CD38 is a protein highly expressed on myeloma (MM) cells that has been shown to be an effective target antigen for monoclonal antibody therapies, so treatment with anti-CD38 monoclonal antibodies is a first line therapy for patients with MM. Although CD38 is weaker expressed on erythocytes anti-CD38 binds to CD38 on reagent RBCs and cause panreactivity in vitro and subsequent false positive reactions in indirect antiglobulin tests (IAT), antibody detection (screening) tests, antibody identification panels, and anti-human globulin (AHG) crossmatches. These findings suggest that the soluble CD38 method could improve transfusion safety for patients receiving anti-CD38 therapy, particularly in urgent clinical settings This study aims to evaluate the effectiveness of a new soluble CD38-based method in mitigating Daratumumab interference during pretransfusion compatibility testing."

Methods: We evaluated the Grifols sCD38 method in 20 patients and compared it with the DTT method

Results: In our experience the sCD38 method reduced testing time from 150 to 50 minutes and demonstrated 100% efficacy, compared to 90% with DTT. The sCD38 effectively mitigated the interference caused by anti-CD38 antibodies in 10 (100% efficacy) of patient samples tested while DTT was successful in only 9/10 (90% efficacy); no interference was observed in patients presenting anti erythrocyte antibodies. Moreover, there was no negative influence on DTT sensitive blood group systems such as KEL upon sCD38 treatment.

Conclusions: In our Laboratory, in the year 2023, we processed 129 patients treated with anti-CD38. Therefore the reduction from 150 to 50 minutes in the time needed to perform tests for mitigation of anti-CD38 interference appears to be relevant with a recovery of approximately 210 technical-hours per year. Another highly appreciated operational aspect was the possibility of treating the patient's plasma and perform tests using automatic instruments (Erytra Grifols) available in our laboratory. In the evaluation of this new method, we did not observe failures in the mitigation of anti-CD38 interference. Furthermore, the results obtained in the samples that presented allo or auto antibodies were not affected by the treatment with sCD38. In our experience Grifols sCD38 assay is straightforward and quick to perform ant it is superior to DTT treatment in the mitigation of anti-CD38 antibody interference in MM patients treated with Daratumumab.