Daratumumab interferes with the evaluation of response. (A) The mean trough and peak serum daratumumab concentrations at the end of weekly 16 mg/kg dosing are 573 μg/mL and 915 μg/mL, respectively.^33,34  These concentrations decrease slightly when patients enter the less-intense dose periods.^33,34  These concentrations are greater than the sensitivity for most SPEP and serum IFE assays, which explains that daratumumab and also other therapeutic antibodies can be detected as a monoclonal band in SPEP and IFE when patients are assessed for response. Comigration of daratumumab (IgG-κ) with an IgG-κ M-protein during SPEP and IFE can mask clearance of a patient’s endogenous M protein in response to treatment. The daratumumab-specific IFE reflex assay (DIRA) uses a highly specific mouse anti-daratumumab antibody that binds daratumumab and shifts its migration away from endogenous M protein on IFE gels. Of note, because the anti-daratumumab antibody is of mouse origin, it is not precipitated with antibodies directed at human immunoglobulins.⁸²  The mouse anti-daratumumab antibody is therefore not detected as an additional band in the DIRA. (B) If an IgG-κ band remains that is not shifted completely by the DIRA, the patient is considered to have residual M protein, and disease monitoring should continue. Patients with a single IgG-κ band that is shifted completely by the DIRA are considered to have no remaining serum M protein and may have reached CR/sCR, and therefore are candidates for additional IMWG-required confirmatory testing (BM evaluation, free light-chain assay). Dara, daratumumab; G, IgG antisera; IHC, immunohistochemistry; κ, κ antisera; sCR, stringent CR; SP, total serum protein fix; VGPR, very-good partial response.