title: CD52 expression in Waldenstrom's macroglobulinemia: implications for alemtuzumab therapy and response assessment.
abstract: The efficacy of monoclonal antibody therapy is determined, at least in part, by the extent to which the target antigen is expressed. This is a complex issue in Waldenstrom's macroglobulinemia (WM) as it is a disorder characterized by plasma cell differentiation and therefore target antigen expression may differ between the B-cell and plasma cell compartments of the disease. In order to assess this in the context of alemtuzumab therapy, the authors used multiparameter flow cytometry to determine CD52 expression in the B-cells and plasma cells of patients with WM. CD52 expression was demonstrable in the B-cells of all cases, with a median of 99% of cells (range, 81%-100%) expressing the antigen compared with the isotype control (n = 47). Antigen density was very similar to that seen in chronic lymphocytic leukemia (median mean fluorescence intensity [MFI], 1249; range, 175-3170). Antigen expression was, however, significantly lower in the plasma cells (median MFI, 235; range, 31-1814) in all but 1 of the cases assessed (n = 21). The clinical significance of this was assessed by examining serial bone marrow samples from patients receiving alemtuzumab as part of an ongoing clinical trial. In 4 of 5 patients, alemtuzumab therapy successfully eradicated clonal B-cells from the bone marrow, but residual plasma cells remained evident in 2 of these patients. The implications of these findings for monoclonal antibody therapy in WM are discussed.
authors.affiliation: Haematological Malignancy Diagnostic Service Laboratory, The Leeds Teaching Hospitals NHS Trust, General Infirmary at Leeds, Great George Street, Leeds LS1 3EX, UK. rgowen@hmds.org.uk
authors.forename: Roger G
authors.initials: RG
authors.lastname: Owen
authors.forename: Peter
authors.initials: P
authors.lastname: Hillmen
authors.forename: Andy C
authors.initials: AC
authors.lastname: Rawstron
mesh_terms: D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000494:pharmacology* / Q000627:therapeutic use*; D015703:Antigens, CD / Q000096:biosynthesis*; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001402:B-Lymphocytes; D001853:Bone Marrow / Q000473:pathology; D000074301:CD52 Antigen; D002454:Cell Differentiation / Q000276:immunology; D005434:Flow Cytometry; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D010950:Plasma Cells; D016896:Treatment Outcome; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D000074323:Alemtuzumab