Godara Amandeep, Siddiqui Nauman Saleem, Lee Lisa X, Toskic Denis, Fogaren Teresa, Varga Cindy, Comenzo Raymond L
John Conant Davis Myeloma and Amyloid Program, Tufts Medical Center, Boston, MA; Division of Hematology-Oncology, Department of Medicine, Tufts Medical Center, Boston, MA.
Division of Hematology-Oncology, Department of Medicine, Tufts Medical Center, Boston, MA.
Clin Lymphoma Myeloma Leuk. 2020 Mar;20(3):184-189. doi: 10.1016/j.clml.2019.10.019. Epub 2020 Jan 2.
Systemic AL amyloidosis (AL) is a rare disease in which clonal immunoglobulin light chains produced by monoclonal plasma cells circulate and misfold, resulting in direct toxicity and fibrillar deposition of amyloid in numerous tissues. Early mortality from cardiac damage remains high. As depth of organ response carries a prognostic significance, combining anti-plasma cell and anti-amyloid therapies might hold the key to achieving long lasting responses. We report a series of patients who received 2 monoclonal antibodies, anti-CD38 and anti-amyloid, simultaneously.
We describe the characteristics and outcomes of 19 patients who received daratumumab (anti-CD38) on progression with front-line therapy for AL, 9 of whom were on concurrent dual monoclonal antibody treatment with daratumumab and NEOD001 (anti-amyloid), and also provide data on the schedule, safety, and tolerability of intravenous infusions of these monoclonal antibodies.
The 9 patients who received treatment with dual monoclonal antibodies achieved a high rate (100%) of hematologic response in a median of 33 days. There was no significant toxicity to dual monoclonal antibody therapy. Seven of the 8 met criteria for cardiac response, achieved in less than 3 months of combined therapy. Ten patients who received daratumumab alone also had high rates of hematologic and organ responses.
Monoclonal antibodies with distinctly different targets can be safely combined in patients with AL and cardiac involvement. Patients experienced high rates of hematologic and cardiac response with combined anti-CD38 and anti-amyloid monoclonal antibody therapies. Further study of this combined approach is warranted.
系统性AL淀粉样变性（AL）是一种罕见疾病，单克隆浆细胞产生的克隆性免疫球蛋白轻链循环并错误折叠，导致淀粉样蛋白在许多组织中直接产生毒性并形成纤维状沉积。心脏损害导致的早期死亡率仍然很高。由于器官反应的深度具有预后意义，联合抗浆细胞和抗淀粉样蛋白疗法可能是实现持久反应的关键。我们报告了一系列同时接受两种单克隆抗体（抗CD38和抗淀粉样蛋白）治疗的患者。
我们描述了19例接受达雷妥尤单抗（抗CD38）治疗且一线治疗进展的AL患者的特征和结局，其中9例同时接受达雷妥尤单抗和NEOD001（抗淀粉样蛋白）的双重单克隆抗体治疗，并提供了这些单克隆抗体静脉输注的方案、安全性和耐受性数据。
接受双重单克隆抗体治疗的9例患者在中位33天内实现了高血液学缓解率（100%）。双重单克隆抗体治疗无明显毒性。8例中有7例达到心脏反应标准，在联合治疗不到3个月时实现。单独接受达雷妥尤单抗治疗的10例患者也有较高的血液学和器官反应率。
具有明显不同靶点的单克隆抗体可安全地联合用于AL和心脏受累患者。联合抗CD38和抗淀粉样蛋白单克隆抗体治疗的患者血液学和心脏反应率较高。有必要对这种联合方法进行进一步研究。
