Jelínek Tomáš, Mihályová Jana, Hájek Roman
Vnitr Lek. 2018 Fall;64(10):939-948.
CD38 antigen is highly and uniformly expressed on plasma cells and thus represents an ideal target for the treatment of multiple myeloma (MM) with anti-CD38 monoclonal antibodies (mAbs). Daratumumab is the most advanced anti-CD38 mAb in the clinical development with approval in several indications, nevertheless isatuximab that targets completely different epitope of CD38 molecule is also very promising drug. Anti-CD38 possess pleiotropic mechanism of action that have been described also in other mAbs, but quite specific, novel and very important seems to be the immunomodulatory effect provided by depletion of several CD38+ immunosuppressive immune cell populations. CD38-targeted mAbs induce partial response or better in approximately 30 % of heavily pre-treated myeloma patients as monotherapy. Based on their favourable toxicity profile and distinct mechanism of action, anti-CD38 mAbs represents very attractive partner to back-bone anti-myeloma drugs. Indeed, daratumumab is already approved as a part of three distinct combination regimens in relapsed setting. The combination of daratumumab with lenalidomide and dexamethasone is considered to be the best treatment option in relapsed myeloma with unprecedented prolongation of median PFS, including high rate of good quality responses. CD38 targeted therapy is rapidly moving toward the first line treatment. Anti-CD38 mAbs have been also successfully tested in other plasma cell dyscrasias (such as AL amyloidosis), and they are examined in other hematological malignancies (such as CLL, ALL, AML, etc.) and even in solid oncology as well as in autoimmune disorders. Implementation of CD38 targeted mAbs have been significant milestone in the treatment of MM, similar to that of CD20 targeted mAbs in CLL or non-Hodgkin lymphomas. We believe that this drug may eventually help to reach the cure at least in a subset of MM patients in the near future. Key words: acute myeloid leukemia - CD38 - daratumumab - isatuximab - multiple myeloma.
CD38抗原在浆细胞上高度且均匀表达,因此是用抗CD38单克隆抗体(mAb)治疗多发性骨髓瘤(MM)的理想靶点。达雷妥尤单抗是临床开发中最先进的抗CD38 mAb,已获批多个适应症,不过,靶向CD38分子完全不同表位的isatuximab也是一种非常有前景的药物。抗CD38具有多效性作用机制,这在其他mAb中也有描述,但相当特殊、新颖且非常重要的似乎是通过消耗多个CD38 +免疫抑制免疫细胞群所提供的免疫调节作用。作为单一疗法,CD38靶向mAb在约30%预处理严重的骨髓瘤患者中可诱导部分缓解或更好的疗效。基于其良好的毒性特征和独特的作用机制,抗CD38 mAb是联合抗骨髓瘤药物的极具吸引力的搭档。事实上,达雷妥尤单抗已获批作为复发情况下三种不同联合方案的一部分。达雷妥尤单抗与来那度胺和地塞米松联合被认为是复发骨髓瘤的最佳治疗选择,可使中位无进展生存期前所未有的延长,包括高质量缓解率高。CD38靶向治疗正迅速走向一线治疗。抗CD38 mAb也已在其他浆细胞疾病(如AL淀粉样变性)中成功测试,并正在其他血液系统恶性肿瘤(如慢性淋巴细胞白血病、急性淋巴细胞白血病、急性髓系白血病等)甚至实体肿瘤学以及自身免疫性疾病中进行研究。CD38靶向mAb的应用是MM治疗中的一个重要里程碑,类似于CD20靶向mAb在慢性淋巴细胞白血病或非霍奇金淋巴瘤中的应用。我们相信,这种药物最终可能至少在一部分MM患者中在不久的将来有助于实现治愈。关键词:急性髓系白血病 - CD38 - 达雷妥尤单抗 - isatuximab - 多发性骨髓瘤