(P-TS-31) Determination of serologic reactivity etiology in the setting of daratumumab cessation

Daratumumab is a CD38-directed monoclonal antibody used to treat multiple myeloma. Daratumumab also binds CD38 on red blood cells (RBCs) and interferes with serologic testing. After daratumumab therapy is stopped, the reactivity pattern may turn from anti-CD38 to negative, which requalifies the patient for electronic crossmatch, or mimic antibodies of undetermined specificity (AUS) before disappearing, requiring serologic crossmatch. The goal of this study was to determine the natural history of serologic testing patterns in the context of daratumumab cessation.


Study

Design/Methods:

This single-center retrospective study included patients who had anti-CD38 from 01/01/2018 to 01/01/2023. Data collected included ABO/Rh type, antibody screens, and antibody identification results and doses of daratumumab administered. Patients who demonstrated anti-CD38 and then progressed to a negative antibody screen or an AUS were included. The time to first negative result after daratumumab administration and the time that the patient sustained a negative result until the last recorded result in the blood bank system or the study timeframe concluded were calculated.


Results/Findings:

Of the 663 patients who received daratumumab and demonstrated anti-CD38, 110 (16.6%) progressed to a negative antibody screen or an AUS. Of the 110 patients, 87 (79.1%) transitioned to a negative antibody screen, 21 (19.1%) transitioned to an AUS, and 2 (1.8%) demonstrated transient negativity despite continued daratumumab treatment. Of the 21 patients who developed an AUS,14 (66.7%) were sustained over time and therefore deemed not associated with daratumumab treatment cessation and 7/21 (33.3%) developed an AUS just prior to converting to a sustained negative antibody status. Of the 14 with sustained AUS, 3/14 (21.4%) developed an RBC alloantibody (anti-E, anti-K, and anti-M).


Conclusions:

Most patients transition directly from anti-CD38 to a negative antibody screen after daratumumab discontinuation, but in some patients daratumumab cessation unmasks AUS reactivity which could be clinically significant, including the formation of RBC alloantibodies. Since true AUS results necessitate serologic crossmatch, clarifying etiology of reactivity by following the pattern over time and developing processes to evaluate sources of reactivity can help guide determination of whether a patient can requalify for electronic crossmatch.