Amyloidosis Research and Treatment Center, Foundation "Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo", 27100 Pavia, Italy.
Department of Molecular Medicine, University of Pavia, 10121 Pavia, Italy.
Cells. 2021 Mar 4;10(3):545. doi: 10.3390/cells10030545.
Systemic light-chain (AL) amyloidosis is caused by a small B cell, most commonly a plasma cell (PC), clone that produces toxic light chains (LC) that cause organ dysfunction and deposits in tissues. Due to the production of amyloidogenic, misfolded LC, AL PCs display peculiar biologic features. The small, indolent plasma cell clone is an ideal target for anti-CD38 immunotherapy. A recent phase III randomized study showed that in newly diagnosed patients, the addition of daratumumab to the standard of care increased the rate and depth of the hematologic response and granted more frequent organ responses. In the relapsed/refractory setting, daratumumab alone or as part of combination regimens gave very promising results. It is likely that daratumumab-based regimens will become new standards of care in AL amyloidosis. Another anti-CD38 monoclonal antibody, isatuximab, is at an earlier stage of development as a treatment for AL amyloidosis. The ability to target CD38 on the amyloid PC offers new powerful tools to treat AL amyloidosis. Future studies should define the preferable agents to combine with daratumumab upfront and in the rescue setting and assess the role of maintenance. In this review, we summarize the rationale for using anti-CD38 antibodies in the treatment of AL amyloidosis.
系统性轻链 (AL) 淀粉样变性由小 B 细胞（通常为浆细胞 [PC]）克隆引起，该克隆产生有毒轻链（LC），导致器官功能障碍和组织沉积。由于产生淀粉样变性、错误折叠的 LC，AL PC 表现出独特的生物学特征。小而惰性的浆细胞克隆是抗 CD38 免疫疗法的理想靶点。最近的一项 III 期随机研究表明，在新诊断的患者中，添加达雷妥尤单抗至标准治疗可增加血液学反应的速度和深度，并获得更频繁的器官反应。在复发/难治性患者中，达雷妥尤单抗单药或联合治疗方案均取得了非常有前景的结果。达雷妥尤单抗为基础的治疗方案很可能成为 AL 淀粉样变性的新标准。另一种抗 CD38 单克隆抗体伊沙妥昔单抗在作为 AL 淀粉样变性的治疗方法方面处于早期开发阶段。靶向淀粉样 PC 上的 CD38 的能力为治疗 AL 淀粉样变性提供了新的有力工具。未来的研究应确定在初始治疗和挽救治疗中与达雷妥尤单抗联合使用的首选药物，并评估维持治疗的作用。在这篇综述中，我们总结了使用抗 CD38 抗体治疗 AL 淀粉样变性的原理。
