Work

Rapid identification of daratumumab interference with M-protein detection using MALDI-TOF mass spectrometry: a case study involving renal light chain amyloidosis

Year: 2025

Type: article

Abstract: : Therapeutic monoclonal antibodies (t-mAbs), such as daratumumab (anti-CD38), are increasingly used in plasma cell disorders including systemic AL amyloidosis. However, their exogenous IgG kappa/lambda components can mimic endogenous monoclonal immunoglobulins in serum immunofixation electrophoresis (IFE), leading to diagnostic challenges. We report a 48-year-old male with biopsy-confirmed lambda-restricted renal AL amyloidosis. After transitioning to daratumumab-CyBorD therapy following CyBorD failure, his serum IFE unexpectedly revealed biclonal bands—a cathodal IgG kappa and anodal IgG lambda—suggesting biclonal gammopathy. Suspecting daratumumab interference (an IgG kappa antibody), we employed mass spectrometry (iMS-LC assay) for definitive analysis. Post-treatment serum showed two distinct peaks (endogenous lambda: m/z 22,718; daratumumab kappa: m/z 23,389), while pre-treatment serum contained only the endogenous lambda peak (m/z 22,716). This confirms daratumumab generates a cathodal IgG kappa band mimicking pathological gammopathy. To prevent diagnostic errors in plasma cell disorder monitoring, laboratories should proactively identify t-mAb interference using historical controls and targeted mass spectrometry.

Source: Practical Laboratory Medicine

DOI: 10.1016/j.plabm.2025.e00493

Authors: Hou-Long Luo, Anping Xu, Ling Ji

Institution: Peking University Shenzhen Hospital

Language: English

Topic: Amyloidosis: Diagnosis, Treatment, Outcomes

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,140