Mitigating the Interference of Daratumumab with Immunofixation Electrophoresis: A Single-center Experience Using the Hydrashift 2/4 Kit

Background: Multiple myeloma (MM] accounts for approximately 10% of hematological malignancies. The monoclonal immunoglobulin G kappa (IgG-K) daratumumab can bind to CD38 on MM cells and be detected in serum immunofixation (IF], causing pitfalls in M-protein quantification. Objectives: To determine the efficacy of mitigating the interference of IgG MM treated with daratumumab. Methods: Levels of Ig, free light chains (FLC] kappa (k) and lambda (λ), serum protein electrophoresis (SPE)/IF, and Hydrashift 2/4 assays were assessed following manufacturer's instructions in three patients. Results: Patient 1 was a 70-year-old male diagnosed with IgG-λ MM. The IF distinguished two monoclonal bands (IgG-K and IgG-λ). With the Hydrashift assay, the daratumumab-anti-da-ratumumab immune complex shifted the IgG-K to the a zone, suggesting that the monoclonal IgG-K band corresponded to daratumumab. Patient 2 was a 63-year-old male with IgG-K MM who was receiving daratumumab once every other week. SPE/ IF assay revealed a faint monoclonal IgG-K band in the y zone. A stronger monoclonal band was observed after administration. The IgG-K band disappeared on the Hydrashift assay, while the daratumumab-anti-daratumumab complex appeared as a broad smear in the a-region. Patient 3, a 63-year-old male diagnosed with IgG-AMM, was receiving daratumumab once every other month. The IF assay showed two distinct bands (IgG-K and IgG-A) post-daratumumab administration. The shift to the a zone of the IgG-K bands on the Hydrashift assay confirmed that the additional band observed post-infusion was due to the daratumumab. Conclusions: The Hydrashift assay can help distinguish daratumumab from endogenous M-spike.