Artifactual Kappa Light Chain Restriction of Marrow Hematogones: A Potential Diagnostic Pitfall in Minimal Residual Disease Assessment of Plasma Cell Myeloma Patients on Daratumumab.

ABSTRACT

BACKGROUND: Daratumumab (DARA) is a humanized Immunoglobulin G(IgG)1-kappa monoclonal antibody against CD38 antigen that is shown to improve outcomes in relapsed/refractory plasma cell myeloma (PCM) patients. Since CD38 is expressed by different hematopoietic elements, DARA has the potential to interfere with flow cytometric assessment of bone marrow specimens. METHODS: Flow cytometric analysis of bone marrow samples from 10 PCM on DARA and 5 control samples was performed using two different antibody panels. RESULTS: Bone marrow samples from PCM patients on DARA exhibited a population of CD19+ CD10+ B-lymphoid cells with kappa light chain restriction. Further morphological and immunophenotypic studies suggested that this population represents marrow hematogones. Marrow hematogones from control samples showed normal immunophenotypic profiles. CONCLUSION: DARA on the surface of hematogones interferes with flow cytometric clonality study leading to artifactual kappa light chain restriction, which can result in false interpretation of a concurrent clonal B-cell proliferation. In the era of rapidly growing list of therapeutic monoclonal antibodies, flow cytometry pathologists should be aware of potential interferences to avoid misdiagnosis. © 2019 International Clinical Cytometry Society.