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从免疫吸附治疗 IgM 多发性骨髓瘤高黏滞血症中吸取的教训——1 例报告。

Lessons learned from immunoadsorption for hyperviscosity in IgM multiple myeloma-A case report.

机构信息

Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, Austria.

Department of Internal Medicine V (Hematology and Oncology), Medical University Innsbruck, Innsbruck, Austria.

出版信息

J Clin Apher. 2020 Jun;35(3):227-230. doi: 10.1002/jca.21775. Epub 2020 Mar 6.

Abstract

We report the case of a 63-year-old Caucasian woman with multiple relapsed IgM multiple myeloma (MM) and elevated free kappa light chains (fκLC). Due to hyperviscosity syndrome with visual impairment, regular plasma exchanges were performed. As part of her 11th line of therapy, an experimental protocol consisting of pembrolizumab, pomalidomide, and dexamethasone was initiated. To reduce fκLC and immunoglobulin (Ig) M, we performed immunoadsorption (IA) using columns containing recombinant single domain camelid antibody fragments as ligands. We measured pembrolizumab (humanized IgG4 kappa anti-PD1 antibody) levels before and after each IA session and found a 98.1% reduction from baseline with five sessions of IA. Comparable elimination kinetics were observed for serum IgG, whereas fκLC and IgM were eliminated to a substantially lesser extent. These findings highlight that in hyperviscosity syndrome due to IgM MM, broad spectrum IA columns might be only moderately effective compared to total plasma exchange or double filtration plasmapheresis. Monoclonal antibodies are efficiently reduced by extracorporeal therapies and re-dosing is necessary to provide sufficient efficacy. In the case of serious adverse events such as immune-related adverse events, IA might be used to eliminate the monoclonal antibody. Measuring IgG levels might be a reasonable strategy for monitoring drug levels of monoclonal antibodies during IA.

摘要

我们报告了一例 63 岁的高加索白人女性,患有复发性 IgM 多发性骨髓瘤(MM)和游离κ轻链(fκLC)升高。由于存在视力损害的高黏滞血症综合征,定期进行血浆置换。作为她的第 11 线治疗方案,启动了一项包含 pembrolizumab、pomalidomide 和地塞米松的实验性方案。为了降低 fκLC 和免疫球蛋白(Ig)M,我们使用含有重组单域骆驼抗体片段作为配体的免疫吸附柱(IA)进行治疗。我们在每次 IA 治疗前后测量了 pembrolizumab(人源化 IgG4 κ抗 PD1 抗体)的水平,发现经过 5 次 IA 治疗后,其水平从基线降低了 98.1%。而 IgG 的消除动力学相似,相比之下,fκLC 和 IgM 的消除程度要小得多。这些发现强调了在 IgM MM 引起的高黏滞血症综合征中,与全血浆置换或双重滤过血浆置换相比,广谱 IA 柱可能只是中度有效。单克隆抗体可被体外治疗有效降低,需要重新给药以提供足够的疗效。在发生严重不良反应(如免疫相关不良反应)的情况下,IA 可能用于消除单克隆抗体。在 IA 期间监测单克隆抗体的药物水平时,测量 IgG 水平可能是一种合理的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/822d/7383619/b5a6e239c9ec/JCA-35-227-g001.jpg

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