Multiple myeloma (MM) is an incurable disease characterized by the presence of malignant plasma cells that secrete high levels of a monoclonal immunoglobulin protein (M-protein). The International Myeloma Working Group (IMWG) has established criteria for clinical response to treatment in MM, which include changes in serum/urine M-protein levels by serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE), percentage of bone marrow plasma cells, and free light chain (FLC) ratios [3–5].
For a patient to be classified as having a complete response (CR) by IMWG criteria, the serum and urine must be negative for M-protein, as determined by IFE and SPE, and bone marrow plasma cells must be ≤ 5%. In serum FLC-only patients, CR is defined as a normal FLC ratio in addition to the other criteria required to classify a CR . For the more robust, deeper classification of stringent complete response (sCR), all of the criteria for CR must be met, along with a normal FLC ratio and absence of clonal plasma cells in the bone marrow, as measured by 2- to 4-color flow cytometry or immunohistochemistry.
To discriminate between endogenous myeloma protein and daratumumab, a daratumumab-specific immunofixation electrophoresis reflex assay (DIRA) was developed using a mouse anti-daratumumab antibody. To evaluate whether anti-daratumumab bound to and shifted the migration pattern of daratumumab, it was spiked into daratumumab-containing serum and resolved by IFE/SPE. The presence (DIRA positive) or absence (DIRA negative) of residual M-protein in daratumumab-treated patient samples was evaluated using predetermined assessment criteria. DIRA was evaluated for specificity, limit of sensitivity, and reproducibility.
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