Anti‐CD20 monoclonal antibody therapy in multiple myeloma

Abstract

SummaryCD20 is a particularly appealing target that is expressed on the surface of almost all B cells, with no significant shedding, secretion or internalization. In contrast to the demonstrated efficacy of anti-CD20 strategies in various B-cell lymphoproliferative disorders, the role of such therapy in multiple myeloma is undetermined and controversial. The expression of CD20 by myeloma cells is heterogeneous, and can be detected only in 13-22% of patients. However, there is increasing interest in testing anti-CD20 therapy in myeloma because of recent studies suggesting the existence of clonogenic CD20-positive precursor B cells in the disease. This article reviews the rationale, preclinical and clinical activity of anti-CD20 therapy in myeloma. Clinical trials show that anti-CD20 therapy with rituximab elicits a partial response in approximately 10% of CD20 + patients with multiple myeloma. In addition, there is preliminary evidence of disease stabilization in 50-57% of CD20 + patients for a period of 10-27 months. Further largescale clinical trials are therefore needed to establish the role of this promising strategy in the treatment of myeloma.

Application of a novel inhibitor of human CD59 for the enhancement of complement-dependent cytolysis on cancer cells

“…However, not all CD20 1 patients respond to rituximab; in fact, only 10% of the CD20 1 patients are responsive. 35 In this paper, we demonstrated that the expression of the complement regulator CD59 is associated with resistance to rituximab-mediated complement lysis in the ARH-77 MM cell line. rILYd4 was effective in abrogating the function of hCD59 in the ARH-77 cell lines.…”

“…35 Recent studies are indicative of the existence of clonogenic CD20-positive precursor B cells in myeloma; thus there is increasing interest in testing anti-CD20 therapies in the disease. 35 In order to test whether rILYd4 enhances the rituximab-mediated CDC effect on MM cells, we used FACS analysis to detect CD20-positive and CD59-postive ARH-77 cells and human MM cells (Figure 2a). We demonstrated that rILYd4 sensitized ARH-77 cells to the CDC effect mediated by rituximab (20 mg/ml) in a dose-dependent manner (Figure 2b).…”

Utility of flow cytometry immunophenotyping in multiple myeloma and other clonal plasma cell‐related disorders

“…(95)(96)(97) In the last decade, MFC immunophenotypic characterization of phenotypically aberrant PC has also been suggested to be a valuable tool for the detection of potential therapeutical targets on clonal PC and orientate tailored antibody-based therapies (and subsequent monitoring). Thus, MoAbs targeting the overall PC population (CD138) (98,99) or either growth factor receptors (IL-6 or IGF-1) (100,101) and other cell surface antigens expressed by aberrant PC (CD33, CD40, CD52, or CD74) (102)(103)(104)(105)(106)(107) and specific markers whose expression is restricted to subsets of PC (e.g. CD19, CD20, CD27, or CD117) have been developed and, several of them are currently under evaluation in phase I/II clinical trials (70,71).…”

Monoklonale Gammopathie unklarer Signifikanz und multiples Myelom

“…[16]. [18]. Aufgrund der geringen CD20-Expression bei MM-Zellen ist der therapeutische Nutzen aber allenfalls minimal in ausgewählten Fällen.…”