Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
Department of Pathology, Emory University, Atlanta, Georgia.
Cancer. 2019 Jul 15;125(14):2364-2382. doi: 10.1002/cncr.32065. Epub 2019 Apr 5.
The development of effective monoclonal antibodies for the treatment of myeloma has been a long journey of clinical and drug development. Identification of the right target antigen was a critical part of the process. CD38 as a target has been considered for some time, but clinically, daratumumab, a CD38 monoclonal antibody, was the first to be tested, and it has delivered the best clinical responses as a single agent to date. Its proven safety and efficacy in combination with other antimyeloma agents have led to several US Food and Drug Administration approvals for treating myeloma. Furthermore, the results of early trials in the induction therapy setting have demonstrated a beneficial role when it is added to the existing induction regimens. This review summarizes the importance of CD38 as a target and examines the clinical development of the CD38 monoclonal antibody daratumumab and its clinical significance in combination regimens in both patients with relapsed/refractory myeloma and patients with newly diagnosed myeloma.
治疗骨髓瘤的有效单克隆抗体的开发是一个漫长的临床和药物开发过程。确定正确的靶抗原是该过程的关键部分。CD38 作为靶标已经被考虑了一段时间，但临床上，CD38 单克隆抗体达雷妥尤单抗是第一个被测试的，并且作为单一药物迄今为止提供了最佳的临床反应。其在与其他骨髓瘤药物联合治疗中的安全性和疗效已获得美国食品和药物管理局的几项批准。此外，诱导治疗方案早期试验的结果表明，当添加到现有诱导方案中时，它具有有益的作用。本文综述了 CD38 作为靶标的重要性，考察了 CD38 单克隆抗体达雷妥尤单抗的临床开发及其在复发性/难治性骨髓瘤患者和新诊断骨髓瘤患者联合治疗方案中的临床意义。
