Gavriatopoulou Maria, Terpos Evangelos, Kastritis Efstathios, Dimopoulos Meletios A
a Department of Clinical Therapeutics , National and Kapodistrian University of Athens, School of Medicine, Alexandra General Hospital , Athens , Greece.
Expert Opin Drug Saf. 2017 Feb;16(2):237-245. doi: 10.1080/14740338.2017.1279603. Epub 2017 Jan 11.
Multiple myeloma (MM) is the second most common hematologic malignancy and despite significant outcome improvements with novel agents, the majority of patients will eventually relapse and develop treatment resistance. Immunotherapy is emerging as a promising therapeutic approach in MM. Areas covered: Elotuzumab is a monoclonal antibody directly targeting the SLAMF7 receptor, expressed on normal and malignant plasma cells. Elotuzumab has no meaningful antimyeloma activity when given as monotherapy to patients with relapsed or refractory MM (RRMM). However, it demonstrated significant antimyeloma activity in preclinical studies and when it is combined with other antimyeloma agents (i.e. bortezomib or lenalidomide) in clinical trials, it improved response and clinical outcomes with no additive toxicity. This review provides a brief description of the elotuzumab mechanism of action and an overview on its efficacy in preclinical and clinical trials, including its safety and toxicity profile. Expert commentary: Based on the results of a phase 3 clinical trial (ELOQUENT-2), which compared lenalidomide and dexamethasone with or without elotuzumab in patients with RRMM, elotuzumab was approved by FDA in November 2015 for MM patients who received 1-3 prior lines of therapy. Studies with combinations of elotuzumab with other anti-myeloma drugs in different phases of MM are ongoing.
多发性骨髓瘤(MM)是第二常见的血液系统恶性肿瘤,尽管新型药物显著改善了治疗效果,但大多数患者最终仍会复发并产生耐药性。免疫疗法正在成为MM中一种有前景的治疗方法。涵盖领域:埃罗妥珠单抗是一种直接靶向信号淋巴细胞激活分子家族成员7(SLAMF7)受体的单克隆抗体,该受体在正常和恶性浆细胞上均有表达。对于复发或难治性MM(RRMM)患者,埃罗妥珠单抗单药治疗时没有显著的抗骨髓瘤活性。然而,它在临床前研究中显示出显著的抗骨髓瘤活性,并且在临床试验中与其他抗骨髓瘤药物(如硼替佐米或来那度胺)联合使用时,提高了缓解率和临床疗效,且没有额外毒性。本综述简要描述了埃罗妥珠单抗的作用机制,并概述了其在临床前和临床试验中的疗效,包括其安全性和毒性特征。专家评论:基于一项3期临床试验(ELOQUENT-2)的结果,该试验比较了来那度胺和地塞米松联合或不联合埃罗妥珠单抗治疗RRMM患者的疗效,埃罗妥珠单抗于2015年11月被美国食品药品监督管理局(FDA)批准用于接受过1 - 3线前期治疗的MM患者。埃罗妥珠单抗与其他抗骨髓瘤药物在MM不同阶段联合使用的研究正在进行中。