Theodorakakou Foteini, Dimopoulos Meletios A, Kastritis Efstathios
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Ther Adv Hematol. 2021 Nov 23;12:20406207211058334. doi: 10.1177/20406207211058334. eCollection 2021.
Primary systemic immunoglobulin light chain (AL) amyloidosis is caused by a plasma cell clone of, usually low, malignant potential that expresses CD38 molecules on their surface. Treatment of AL amyloidosis is based on the elimination of the plasma cell clone. The combination of cyclophosphamide-bortezomib-dexamethasone (CyBorD) is the most widely used and is considered a standard of care; however, complete hematologic response rates and organ response rates remain unsatisfactory. Daratumumab, an anti-CD38 monoclonal antibody, has demonstrated encouraging results, with rapid and deep responses, in patients with relapsed or refractory AL amyloidosis as monotherapy with a favorable toxicity profile. The large phase-III, randomized, ANDROMEDA study evaluated the addition of daratumumab to CyBorD in previously untreated patients with AL amyloidosis and demonstrated that addition of daratumumab can substantially improve hematologic complete response rates, survival free from major organ deterioration or hematologic progression, and organ responses. In this review, we discuss the role of daratumumab in the treatment of AL amyloidosis, its mechanism of action, and the results of ANDROMEDA study that led to the first approved therapy for AL amyloidosis.
原发性系统性免疫球蛋白轻链（AL）淀粉样变性由通常具有低恶性潜能的浆细胞克隆引起，这些浆细胞在其表面表达CD38分子。AL淀粉样变性的治疗基于消除浆细胞克隆。环磷酰胺-硼替佐米-地塞米松（CyBorD）联合方案是使用最广泛的，被视为标准治疗方案；然而，完全血液学缓解率和器官缓解率仍不尽人意。达雷妥尤单抗是一种抗CD38单克隆抗体，在复发或难治性AL淀粉样变性患者中作为单药治疗，已显示出令人鼓舞的结果，具有快速且深度的缓解，且毒性特征良好。大型III期随机ANDROMEDA研究评估了在先前未治疗的AL淀粉样变性患者中，将达雷妥尤单抗添加到CyBorD方案中的疗效，结果表明添加达雷妥尤单抗可显著提高血液学完全缓解率、无主要器官恶化或血液学进展的生存率以及器官缓解率。在本综述中，我们讨论了达雷妥尤单抗在AL淀粉样变性治疗中的作用、其作用机制以及ANDROMEDA研究的结果，该研究促成了首个获批用于AL淀粉样变性的治疗方法。
