Daratumumab resistance is frequent in advanced-stage multiple myeloma patients irrespective of CD38 expression and is related to dismal prognosis
Daratumumab resistance is frequent in advanced-stage multiple myeloma patients irrespective of CD38 expression and is related to dismal prognosis
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DOI：
10.1111/ejh.13046
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发表时间：
2018-05-01
影响因子：
3.1
通讯作者：
Gatt, Moshe E.
中科院分区：
文献类型：
--
作者：
Pick, Marjorie;Vainstein, Vladimir;Gatt, Moshe E.
目的：达雷妥尤单抗是一种很有前途的新型抗骨髓瘤药物。我们报告了一个单中心的“真实世界”系列的多发性骨髓瘤（MM）和淀粉样变性（AL）患者治疗daratumumab.Methods：41例患者包括：7个二线MM，30个重度预治疗（治疗的中位数为5）晚期MM，和4个AL。然而，晚期MM患者的预后较差，总缓解率（ORR）为36%，中位无进展生存期和总生存期分别为2.3和6.6个月。髓外浆细胞瘤患者的反应尤其差。在该患者人群中，在达雷妥尤单抗基础上添加另一种药物或变更为下一线治疗均未产生显著的持久缓解。流式细胞术分析表明，CD38表达水平不能预测缓解。我们表明，CD38的表达动力学的市售抗CD38抗体后，达雷妥尤单抗管理受到阻碍的竞争性bindingofdaratumumab.Conclusions：反应达雷妥尤单抗和组合在晚期MM患者，特别是髓外疾病，是低和短暂的，强调这种药物的管理应在病程的早期。
Objective: Daratumumab is a promising new antimyeloma agent. We report a single center "real-world" series of multiple myeloma (MM) and amyloidosis (AL) patients treated with daratumumab.Methods: Forty-one patients were included: 7 second-line MM, 30 heavily pre-treated (median number of therapies of 5) advanced MM, and 4 with AL.Results: Second-line patients and advanced AL showed high rate of durable overall responses. However, advanced MM patients had a dismal prognosis with an overall response rate (ORR) of 36%, and a short median progression-free and overall survival of 2.3 and 6.6 months, respectively. Responses were particularly poor in patients with extramedullary plasmacytomas. Neither the addition of another agent to daratumumab nor changing to the next line of therapy produced significant durable responses in this patient population. Flow cytometry analysis demonstrated that CD38 expression level was not predictive of response. We show that CD38 expression dynamics by a commercially available anti-CD38 antibody after daratumumab administration was hindered by competitive binding of daratumumab.Conclusions: Responses to daratumumab and combinations in patients with advanced MM, particularly with extramedullary disease, are low and short-lived, stressing the administration of this agent should be early in the course of the disease.