Assessing Clinical Response In Multiple Myeloma (Mm) Patients Treated With Monoclonal Antibodies (Mabs): Validation Of A Daratumumab Ife Reflex Assay (Dira) To Distinguish Malignant M-Protein From Therapeutic Antibody.

8590 Background: Residual therapeutic mAbs can be detected by assays intended to monitor clonal myeloma protein (M-protein). Daratumumab, a human anti-CD38 IgG1k mAb in MM clinical trials, has been detected on serum protein electrophoresis (SPE) and immunofixation (IFE) gels, interfering with IMWG response criteria requiring negative SPE/IFE for CR/sCR. As new therapeutics emerge that induce very deep responses a method is needed to confirm CR/sCR. Validation and use in clinical studies of an assay that distinguishes daratumumab from M-protein is presented. Methods: Mouse anti-daratumumab antibody is used to shift daratumumab’s IFE migration away from M-protein. Commercial and daratumumab-treated MM patient samples were evaluated to assess specificity, reproducibility and concordance. Detection of M-protein depletion by DIRA triggered additional clinical testing to confirm CR/sCR. Results: Daratumumab was identified on IFE in 10/10 samples when added to commercial MM serum in a 1:1 ratio with anti-daratum...