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

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: <i>m</i>/<i>z</i> 22,718; daratumumab kappa: <i>m</i>/<i>z</i> 23,389), while pre-treatment serum contained only the endogenous lambda peak (<i>m</i>/<i>z</i> 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.