RESUMEN
Daratumumab is a fully human anti-CD38 IgG1-κ monoclonal antibody (mAb) currently being evaluated in several Phase 2 and 3 clinical studies for the treatment of multiple myeloma (MM). In this clinical case study we demonstrate that daratumumab can be detected as an individual monoclonal band in serum immunofixation electrophoresis (IFE). M-protein follow-up by IFE is part of the International Myeloma Working Group (IMWG) criteria to assess treatment response. Therefore, it is crucial that the daratumumab band is not confused with the endogenous M-protein of the patient during IFE interpretation. Moreover, a significant number of IgG-κ M-proteins co-migrate with daratumumab. Co-migration introduces a bias in the M-protein quantification since pharmacokinetic studies show that daratumumab peak plasma concentrations reach up to 1 g/L. More importantly, co-migration can mask clearance of the M-protein by IFE which is necessary for classification of complete response by IMWG criteria (negative serum IFE). For optimal M-protein monitoring the laboratory specialist needs to be informed when patients receive daratumumab, and it is essential that the laboratory specialist is aware that a slow migrating band in the γ-region in those patients may be derived from the daratumumab. A daratumumab specific IFE reflex assay (DIRA) has been developed and can be utilized to abrogate interference. The here described mAb interference is not limited to daratumumab, and as therapeutic antibodies gain approval and enter into common clinical practice, laboratory specialists will need additional processes to characterize IFE interference and distinguish endogenous M-protein from therapeutic antibodies.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Inmunoensayo/métodos , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Anciano , Electroforesis de las Proteínas Sanguíneas , Reacciones Cruzadas , Humanos , Inmunoelectroforesis , Inmunoglobulina G/sangre , Cadenas kappa de Inmunoglobulina/sangre , Cadenas lambda de Inmunoglobulina/sangre , Masculino , Persona de Mediana Edad , Mieloma Múltiple/inmunología , Proteínas de Mieloma/análisisRESUMEN
An 81-year-old woman was referred for darkly pigmented corneal lesions affecting the corneal endothelium and stroma after uncomplicated right cataract surgery 2 years earlier. She was being treated with maintenance loteprednol, 0.5%, eye drops for persistent low-grade anterior uveitis. What would you do next?