Clin Chem Lab Med. 2016 Jun 1;54(6):1105-9. doi: 10.1515/cclm-2015-0888.
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.
达雷妥尤单抗是一种完全人源抗 CD38 IgG1-κ 单克隆抗体（mAb），目前正在多项 2 期和 3 期临床试验中评估，用于治疗多发性骨髓瘤（MM）。在这项临床病例研究中，我们证明达雷妥尤单抗可以在血清免疫固定电泳（IFE）中作为单个单克隆条带被检测到。M 蛋白的 IFE 随访是国际骨髓瘤工作组（IMWG）评估治疗反应标准的一部分。因此，在 IFE 解释过程中，至关重要的是不要将达雷妥尤单抗条带与患者的内源性 M 蛋白混淆。此外，相当数量的 IgG-κ M 蛋白与达雷妥尤单抗共迁移。共迁移会导致 M 蛋白定量产生偏差，因为药代动力学研究表明，达雷妥尤单抗的血浆峰浓度可达到 1g/L。更重要的是，共迁移会掩盖 IFE 对 M 蛋白清除的作用，而这是 IMWG 标准（IFE 阴性血清）分类完全缓解所必需的。为了实现最佳的 M 蛋白监测，当患者接受达雷妥尤单抗治疗时，实验室专家需要得到通知，实验室专家必须意识到，在这些患者中，γ 区迁移缓慢的条带可能来自达雷妥尤单抗。已经开发了一种达雷妥尤单抗特异性 IFE 反射检测（DIRA），并可用于消除干扰。这里描述的 mAb 干扰不仅限于达雷妥尤单抗，随着治疗性抗体获得批准并进入常规临床实践，实验室专家将需要额外的流程来描述 IFE 干扰，并将内源性 M 蛋白与治疗性抗体区分开来。
