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Rapid identification of daratumumab interference with M-protein detection using MALDI-TOF mass spectrometry: a case

Hou-Long Luo1,2, Anping Xu1,2, Ling Ji1,2

  • 1Department of Laboratory Medicine, Peking University Shenzhen Hospital, 1120 Lianhua Road Futian, Shenzhen, Guangdong, 518036, PR China.

Practical Laboratory Medicine
|July 24, 2025
PubMed

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.

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