Magen Hila, Muchtar Eli
Institute of Hematology, Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center, Petah-Tikva, Israel.
Division of Hematology, Mayo Clinic, Rochester, MN, USA.
Ther Adv Hematol. 2016 Aug;7(4):187-95. doi: 10.1177/2040620716652862. Epub 2016 Jun 10.
Elotuzumab is a monoclonal antibody directed against the SLAMF7 receptor, expressed on normal and malignant plasma cells with a lower expression on other lymphoid cells such as natural killer (NK) cells. Elotuzumab has no significant antimyeloma activity when given as a single agent to patients with relapsed or refractory multiple myeloma (RRMM). However, when combined with other antimyeloma agents, it results in improved response and outcome. Owing to the results from the landmark ELOQUENT-2 phase III clinical trial, which compared lenalidomide and dexamethasone with or without elotuzumab in patients with RRMM, elotuzumab in combination with lenalidomide and dexamethasone was approved by the American Food and Drug Administration (FDA) in November 2015 for multiple myeloma (MM) patients who received one to three prior lines of therapy. This review will give a brief description of the signaling lymphocytic activation molecule (SLAM) family receptors, the unique SLAMF7 receptor and the mechanism of action of elotuzumab. Thereafter, we will give an overview on its antimyeloma activity in preclinical and clinical trials, including its toxicity profile and management thereof.
埃罗妥珠单抗是一种针对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表达,而在其他淋巴细胞(如自然杀伤细胞)上表达较低。对于复发或难治性多发性骨髓瘤(RRMM)患者,单独使用埃罗妥珠单抗时没有显著的抗骨髓瘤活性。然而,当与其他抗骨髓瘤药物联合使用时,它能改善疗效和预后。由于具有里程碑意义的III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,埃罗妥珠单抗联合来那度胺和地塞米松于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至3线前期治疗的多发性骨髓瘤(MM)患者。本综述将简要描述信号淋巴细胞激活分子(SLAM)家族受体、独特的SLAMF7受体以及埃罗妥珠单抗的作用机制。此后,我们将概述其在临床前和临床试验中的抗骨髓瘤活性,包括其毒性特征及处理方法。