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

Background: Rituximab has been used to treat relapsed low-grade or advanced non-Hodgkin's lymphoma since 1997, targeting the CD20 antigen expressed by B cells. Single-agent rituximab therapy is safe and well tolerated. Recurrences showing a loss of CD20 expression following rituximab therapy have been reported. Methods: Four patients with CD20-positive cutaneous B-cell lymphoma received rituximab therapy with subsequent recurrences. The biopsies were assessed for cytoplasmic CD20 expression; CD20 messenger RNA was also assessed where tissue was available. Results: Cutaneous relapses occurring within 1.5-3 months following the last dose of rituximab were CD20 negative. In three cases, subsequent relapses showed renewed expression of CD20. Those biopsies demonstrating a loss of surface and cytoplasmic CD20 by immunohistochemistry also showed no evidence of messenger RNA for CD20 using an in situ polymerase chain reaction-based methodology. Conclusions: 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.