Loss of CD20 Expression with Rituximab Appears Transitory

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From 2002 ASH

[3174] Transient Downmodulation of CD20 by Rituximab.

Iman Jilani, O'Brien, Taghi Manshouri, Deborah A. ,

Vilmos A. Thomazy, Maha Imam, Sana Naeem, Srdan Verstovsek, Hagop

Kantarjian, Francis Giles, Keating, Maher Albitar.

Hematopathology, University of Texas MD Cancer Center,

Houston, TX, USA; Leukemia, University of Texas MD Cancer

Center, Houston, TX, USA

Rituximab is a chimeric monoclonal antibody targeting CD20 and used

in the treatment of B-cell lymphomas and chronic lymphocytic leukemia

(CLL). Despite the relative success of rituximab in treating these

diseases, there is a need for optimizing dosing and scheduling of

therapy.

Lymphoid cells in CLL patients treated on protocols including

rituximab become CD20 negative and this is presumed to be due to

masking of CD20 by the rituximab. We used specific anti-mouse

immunoglobulin antibodies for the detection of rituximab on the

surface of cells and demonstrated that rituximab is rarely detectable

on the surface of CLL cells after therapy with rituximab. Only 2 of

65 CLL patients had detectable rituximab on the surface of their

cells despite lack of CD20 expression after the treatment with

rituximab.

Two patients with acute lymphoblastic leukemia treated with

chemotherapy and rituximab became negative for both rituximab and

CD20 within 24 hours of therapy.

In vitro mixing of CLL or Raji cells with rituximab demonstrated that

rituximab is detectable on the surface of cells due to binding to

CD20. However, adding plasma to these mixtures leads to

downmodulation of CD20 expression and rituximab becomes undetectable.

This downmodulation of CD20 protein expression is associated with

downmodulation of CD20 mRNA as detected by real-time reverse

transcription and polymerase chain reaction.

CLL cells that lose their CD20 expression after exposure to rituximab

regain CD20 expression upon culturing without rituximab for 24 hours.

This data suggest that rituximab therapy leads to substantial

downmodulation of CD20 expression and negativity for CD20 in patients

treated with rituximab is not necessarily due to CD20 masking.

However, CD20 downmodulation appears to be transient, the importance

of this downmodulation should be further investigated and addressed

in dosing and scheduling of rituximab therapy.