The absence of CD20 messenger RNA in recurrent cutaneous B‐cell lymphoma following rituximab therapy

Abstract

Rituximab may be associated with the emergence of CD20-negative B-cell clones, potentially rendering a tumor insensitive to this drug. Conversely, following cessation of the drug, a re-expression of CD20 within the neoplastic cells may occur allowing therapeutic intervention with this monoclonal antibody. The loss of CD20 expression appears to be a direct effect of the drug on CD20 messenger RNA synthesis.

Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial

“…This occurs primarily a few weeks after cessation of therapy. 17 However, whether patients who are progressive or nonresponding on first-line treatment will have the same beneficial effects of rituximab as observed in the present study is uncertain. On the one hand it is conceivable that the sensitizing effects of rituximab only become significant when it is coadministered with an effective second-line chemotherapy regimen.…”

Interindividual Variability of Response to Rituximab: From Biological Origins to Individualized Therapies

“…Hiraga and colleagues (33) recently presented evidence that epigenetic mechanisms may be partly related to the downregulation of CD20 expression after rituximab treatment, but to date there is no evidence that CD20 downregulation is an underlying cause of rituximab-refractory disease. In several case reports and small series, investigators have examined the development of CD20-negative phenotypes after treatment of CD20-positive lymphoma in different clinical settings, but the frequency with which this occurs still is unclear (33)(34)(35)(36)(37)(38)(39).…”

Down-regulation of CD20 expression in B-cell lymphoma cells after treatment with rituximab-containing combination chemotherapies: its prevalence and clinical significance

“…Several mechanisms of resistance were predicted as reported previously, including loss of CD20 expression, inhibition of antibody binding, antibody metabolism, expression of complement inhibitors such as CD55/CD59, and membrane/ lipid raft abnormality (reviewed by Smith et al 9 ), [10][11][12][13][14][15][16][17][18][19] but the clinical significance of those mechanisms has remained unclear. In the last 5 years, a CD20-negative phenotypic change in CD20-positive lymphomas after rituximab treatment has been reported by several groups, 16,[20][21][22][23][24][25][26][27][28][29][30][31] indicating that this phenomenon after the use of rituximab may not be rare. Although these reports contain important information from clinical experiences, the frequency of occurrence and detailed molecular biologic information about the CD20-negative phenotype remain to be elucidated.…”