Laboratory diagnostic in multiple myeloma: Quantification of daratumumab blood levels using isoelectric focusing

Therapeutic monoclonal antibodies (tmAbs) such as daratumumab (DmAb) are among the primary treatment options for multiple myeloma. The availability of immunoassays for measuring tmAb blood levels is limited, although determining antibody concentrations may be of interest in cases of unexpected clinical outcomes. As has previously been demonstrated, isoelectric focusing (IEF) can be used to identify tmAbs and their differentiation from paraproteins. Here, the use of IEF for measuring tmAb concentrations is further expanded.

First, a DmAb standard series ranging from 2.5 to 0.08 mg/L spiked with a polyclonal IgG background of 2.5 mg/L was defined and evaluated. After establishing the standard series, the DmAb concentrations were analyzed in patient blood samples collected one to five weeks post-administration, depending on the time after administration and the corresponding therapy phase.

DmAb concentrations stabilized three to four weeks after administration. Within a therapy cycle, profound differences in DmAb levels were observed when comparing the induction, consolidation and maintenance phase.

IEF is a suitable tool for evaluating blood concentrations of DmAb and possibly other tmAbs in case of challenging therapy response.