Radhakrishnan Sabarinath Venniyil, Bhardwaj Neelam, Steinbach Mary, Weidner Janet, Luetkens Tim, Atanackovic Djordje
a Multiple Myeloma Program & Cancer Immunotherapy , Hematology and Hematologic Malignancies, University of Utah / Huntsman Cancer Institute , Salt Lake City , UT , USA.
Hum Vaccin Immunother. 2017 Aug 3;13(8):1751-1757. doi: 10.1080/21645515.2017.1327487. Epub 2017 Jun 12.
Treatment of multiple myeloma has undergone significant change in the last decade with the introduction of new immunomodulatory agents, proteasome inhibitors, and immunotherapeutic approaches. Elotuzumab is a humanized monoclonal antibody targeting CS1, which is a member of the SLAM (Signaling Lymphocyte Activation Molecule) family of proteins, expressed on the surface of myeloma plasma cells. Here we review the preclinical investigations that led to the development of elotuzumab and the clinical studies that resulted in its approval for the treatment of relapsed/refractory multiple myeloma. Although preclinical data looked very promising, elotuzumab monotherapy did not result in objective clinical responses in patients with relapsed/refractory multiple myeloma. However, combination treatment with immunomodulators and proteasome inhibitors resulted in substantial clinical activity in relapsed/refractory MM. Currently, there are several clinical trials ongoing investigating the role of elotuzumab in newly diagnosed myeloma patients and in patients receiving maintenance therapy.
在过去十年中,随着新型免疫调节剂、蛋白酶体抑制剂和免疫治疗方法的引入,多发性骨髓瘤的治疗发生了显著变化。埃罗妥珠单抗是一种靶向CS1的人源化单克隆抗体,CS1是信号淋巴细胞激活分子(SLAM)蛋白家族的成员,在骨髓瘤浆细胞表面表达。在此,我们回顾了促成埃罗妥珠单抗研发的临床前研究以及使其获批用于治疗复发/难治性多发性骨髓瘤的临床研究。尽管临床前数据看起来非常有前景,但埃罗妥珠单抗单药治疗在复发/难治性多发性骨髓瘤患者中并未产生客观的临床反应。然而,与免疫调节剂和蛋白酶体抑制剂联合治疗在复发/难治性多发性骨髓瘤中产生了显著的临床活性。目前,有几项正在进行的临床试验在研究埃罗妥珠单抗在新诊断的骨髓瘤患者和接受维持治疗的患者中的作用。