Department of Haematooncology, University Hospital Ostrava and Faculty of Medicine, Ostrava, Czech Republic.
Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
Br J Haematol. 2020 Apr;189(2):228-238. doi: 10.1111/bjh.16436. Epub 2020 Feb 18.
Immunoglobulin light-chain amyloidosis (AL amyloidosis) is a rare disease in which a small plasma cell clone produces toxic misfolded proteins that deposit in organs and impair their function. Currently, the only available treatment approach is the elimination of clonal plasma cells. However, a rapid strike that halts and possibly reverses organ damage is crucial. The development of agents that facilitate the clearance of pathological fibrillar deposits, therefore reducing the frailty of patients, is the needed supplement to plasma cell-directed therapy. Monoclonal antibodies provide therapy against malignant plasma cells (daratumumab, isatuximab, elotuzumab) but they are also able to target and eliminate the amyloid from organs (NEOD001, CAEL-101, dezamizumab). From the plasma cell-directed group, daratumumab in monotherapy has proved to be extremely efficient in relapsed AL amyloidosis, exceeding its results in multiple myeloma. Compared to other agents, monoclonal antibodies possess the advantage of high selectivity and low toxicity and could potentially become future game-changers in this field. Co-targetting of the plasma cell clone and amyloid deposits shall together be translated in the revolutionary improved outcome of potentially curable AL amyloidosis.
免疫球蛋白轻链淀粉样变性（AL 淀粉样变性）是一种罕见的疾病，其中一个小浆细胞克隆产生有毒的错误折叠蛋白，这些蛋白在器官中沉积并损害其功能。目前，唯一可用的治疗方法是消除克隆性浆细胞。然而，迅速阻止并可能逆转器官损伤是至关重要的。开发有助于清除病理性纤维状沉积物的药物，从而降低患者的脆弱性，是对浆细胞定向治疗的必要补充。单克隆抗体提供针对恶性浆细胞的治疗（达雷妥尤单抗、伊沙妥昔单抗、埃罗妥珠单抗），但它们也能够靶向并消除器官中的淀粉样蛋白（NEOD001、CAEL-101、德扎鲁单抗）。在单药治疗中，达雷妥尤单抗已被证明在复发性 AL 淀粉样变性中非常有效，其疗效超过多发性骨髓瘤。与其他药物相比，单克隆抗体具有高选择性和低毒性的优势，有可能成为该领域的未来变革者。浆细胞克隆和淀粉样沉积物的共同靶向治疗将共同转化为潜在可治愈的 AL 淀粉样变性的革命性改善结局。
