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New developments in the treatment of multiple myeloma – clinical utility of daratumumab

机译:多发性骨髓瘤治疗的新进展– daratumumab的临床应用

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摘要

Multiple myeloma is a clonal disorder of plasma cells that is currently considered incurable. CD38 is a 46 kDa type II transmembrane glycoprotein that is highly expressed on myeloma cells. Daratumumab is a first in-class human IgG1 monoclonal antibody that targets CD38, and has antimyeloma effects through several mechanisms. Single-agent trials show surprising activity in heavily pretreated myeloma patients. Trials in the relapsed setting, where daratumumab is added to lenalidomide and dexamethasone or bortezomib and dexamethasone, have demonstrated significantly improved progression-free survival with acceptable toxicity. In this review, we discuss the mechanism of action, pharmacology and pharmacokinetics of daratumumab and review the available clinical data in detail. We examine how daratumumab interferes with transfusion testing due to the expression of CD38 on the red blood cells, leading to potential difficulties releasing blood products. Daratumumab also affects disease assessments in multiple myeloma, including serum protein electrophoresis, immunofixation and flow cytometry. Strategies to mitigate these effects are discussed. The optimal use of daratumumab has yet to be decided, and several trials are ongoing in the relapsed and upfront setting. We discuss the potential upfront role of this exciting therapy, which has significant potential for increased minimal residual disease negativity and improved progression-free survival even in high-risk groups.
机译:多发性骨髓瘤是浆细胞的克隆性疾病,目前被认为是无法治愈的。 CD38是一种46 kDa II型跨膜糖蛋白,在骨髓瘤细胞上高度表达。 Daratumumab是第一个针对CD38的同类人类IgG1单克隆抗体,并通过多种机制具有抗骨髓瘤作用。单药试验显示,在大量预处理的骨髓瘤患者中,其活性令人惊讶。在复发环境中的试验中,将来那度单抗加到来那度胺和地塞米松或硼替佐米和地塞米松中,已证明无进展生存期显着改善,毒性可接受。在这篇综述中,我们讨论了daratumumab的作用机理,药理作用和药代动力学,并详细综述了可用的临床数据。我们检查了daratumumab如何由于红细胞上CD38的表达而干扰输血测试,从而导致释放血液制品的潜在困难。 Daratumumab还影响多发性骨髓瘤的疾病评估,包括血清蛋白电泳,免疫固定和流式细胞仪。讨论了减轻这些影响的策略。 daratumumab的最佳用法尚未确定,并且在复发和前期环境中正在进行多项试验。我们讨论了这种令人兴奋的疗法的潜在前期作用,即使在高危人群中,该疗法也具有显着的潜力,可增加最小的残留疾病阴性率并改善无进展生存期。

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