Morè Sonia, Petrucci Maria Teresa, Corvatta Laura, Fazio Francesca, Offidani Massimo, Olivieri Attilio
Clinica di Ematologia, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, 60126 Ancona, Italy.
Sezione di Ematologia, Dipartimento di Medicina Traslazionale e di Precisione, Azienda Ospedaliera Policlinico Umberto I, Università "Sapienza" di Roma, 00161 Roma, Italy.
Pharmaceuticals (Basel). 2020 Nov 27;13(12):426. doi: 10.3390/ph13120426.
Multiple myeloma is a complex hematologic malignancy, and despite a survival improvement related to the growing number of available therapeutic options since 2000s, it remains an incurable disease with most patients experiencing relapse. However, therapeutic options for this disease are constantly evolving and immunotherapy is becoming the mainstay of the therapeutic armamentarium of Multiple Myeloma (MM), starting with monoclonal antibodies (MoAbs) as elotuzumab, daratumumab and isatuximab. Elotuzumab, the first in class targeting SLAMF7, in combination with lenalidomide and dexamethasone and daratumumab, directed against CD38, in combination with Rd and with bortezomib and dexamethasone (Vd), have been approved for the treatment of relapsed/refractory MM (RRMM) after they demonstrated excellent efficacy. More recently, another anti-CD38 MoAb named isatuximab was approved by FDA in combination with pomalidomide-dexamethasone (Pd) in the same setting. Many phase II and III trials with regimens containing these MoAbs are ongoing, and when available, preliminary data are very encouraging. In this review we will describe the results of major clinical studies that have been conducted with elotuzumab, daratumumab and isatuximab in RRMM, focusing on phase III trials. Moreover, we will summarized the emerging MoAbs-based combinations in the RRMM landscape.
多发性骨髓瘤是一种复杂的血液系统恶性肿瘤，尽管自21世纪以来，随着可用治疗方案数量的增加，患者生存率有所提高，但它仍然是一种无法治愈的疾病，大多数患者会复发。然而，这种疾病的治疗方案在不断发展，免疫疗法正成为多发性骨髓瘤（MM）治疗手段的主流，首先是单克隆抗体（MoAbs），如埃罗妥珠单抗、达雷妥尤单抗和isatuximab。埃罗妥珠单抗是首个靶向信号淋巴细胞激活分子家族成员7（SLAMF7）的药物，与来那度胺和地塞米松联合使用；达雷妥尤单抗靶向CD38，与来那度胺和地塞米松联合使用（Rd方案）以及与硼替佐米和地塞米松联合使用（Vd方案），在显示出卓越疗效后，已被批准用于治疗复发/难治性多发性骨髓瘤（RRMM）。最近，另一种名为isatuximab的抗CD38单克隆抗体也被美国食品药品监督管理局（FDA）批准，与泊马度胺 - 地塞米松（Pd方案）联合用于相同情况。许多包含这些单克隆抗体的方案的II期和III期试验正在进行中，一旦有可用数据，初步数据非常令人鼓舞。在本综述中，我们将描述在RRMM中使用埃罗妥珠单抗、达雷妥尤单抗和isatuximab进行的主要临床研究结果，重点关注III期试验。此外，我们将总结RRMM领域中基于单克隆抗体的新兴联合治疗方案。
