治疗性单克隆抗体干扰在单克隆丙种球蛋白病监测中的发生率和处理。

Incidence and Management of Therapeutic Monoclonal Antibody Interference in Monoclonal Gammopathy Monitoring.

机构信息

Department of Pathology, Division of Clinical Immunopathology, University of Pittsburgh Medical Center, Pittsburgh, PA.

Department of Enterprise Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA.

出版信息

J Appl Lab Med. 2020 Jan 1;5(1):29-40. doi: 10.1373/jalm.2019.029009.

DOI:10.1373/jalm.2019.029009

PMID:32445341

Abstract

BACKGROUND

The treatment of multiple myeloma (MM) has been revolutionized by the introduction of therapeutic monoclonal antibodies (tmAbs). Daratumumab, a human IgG1/κ tmAb against CD38 on plasma cells, has improved overall survival in refractory MM and was recently approved as a frontline therapy for MM. Work on tmAb interference with serum protein electrophoresis (SPE) during MM monitoring has failed to provide information for laboratories on incidence of interference and effective methods of managing the interference at a practicable level. We aimed to evaluate daratumumab and elotuzumab interference in a large academic hospital setting and implement immediate solutions.

METHODS

We identified and chart reviewed all cases of possible daratumumab interference by electrophoretic pattern (120 of 1317 total cases over 3 months). We retrospectively reviewed SPE cases in our laboratory to assess clinical implications of tmAb interference before the laboratory was aware of tmAb treatment. We supplemented samples with daratumumab and elotuzumab to determine the limits of detection and run free light chain analysis.

RESULTS

Approximately 9% (120 of 1317) of tested cases have an SPE and/or immunofixation electrophoresis (IFE) pattern consistent with daratumumab, but only approximately 47% (56) of these cases were associated with daratumumab therapy. Presence of daratumumab led to physician misinterpretation of SPE/IFE results. Limits of daratumumab detection varied with total serum gammaglobulin concentrations, but serum free light chain analysis was unaffected.

CONCLUSIONS

Clinical laboratories currently rely on interference identification by electrophoretic pattern, which may be insufficient and is inefficient. Critical tools in preventing misinterpretation efficiently include physician education, pharmacy notifications, separate order codes, and interpretive comments.

摘要

背景

治疗多发性骨髓瘤（MM）的方法已经因治疗性单克隆抗体（tmAb）的引入而发生了革命性变化。达雷妥尤单抗是一种针对浆细胞上 CD38 的人源 IgG1/κ tmAb，已改善了难治性 MM 的总生存期，最近被批准作为 MM 的一线治疗药物。在 MM 监测过程中，tmAb 对血清蛋白电泳（SPE）的干扰研究未能为实验室提供有关干扰发生率和在可行水平上有效管理干扰的信息。我们旨在评估达雷妥尤单抗和依洛尤单抗在大型学术医院环境中的干扰，并立即提出解决方案。

方法

我们通过电泳模式（3 个月内共 1317 例总病例中的 120 例）确定并图表回顾了所有可能存在达雷妥尤单抗干扰的病例。我们回顾性地审查了我们实验室的 SPE 病例，以评估实验室意识到 tmAb 治疗之前 tmAb 干扰的临床意义。我们补充了达雷妥尤单抗和依洛尤单抗的样本，以确定检测限并进行游离轻链分析。

结果

约 9%（1317 例检测病例中的 120 例）的 SPE 和/或免疫固定电泳（IFE）模式与达雷妥尤单抗一致，但只有约 47%（56 例）的这些病例与达雷妥尤单抗治疗有关。达雷妥尤单抗的存在导致医生对 SPE/IFE 结果的错误解读。达雷妥尤单抗的检测限因总血清球蛋白浓度而异，但血清游离轻链分析不受影响。