Loss of CD20 expression in relapsed lymphomas after rituximab therapy

Abstract

The response rate at relapse to rituximab in prior responders B-cell non-Hodgkin's lymphoma (NHL) patients is below 50%. Loss of CD20 expression after rituximab therapy may explain this secondary resistance. However, the frequency of CD20 negative relapses cannot be assessed since most patients that relapsed after rituximab therapy have not been re-biopsied. Here, we present two patients with CD20 positive low grade B-cell NHL that lost the cell surface and cytoplasmic expression at relapse after rituximab therapy. Our findings suggest that confirmation of CD20 expression on the malignant B cells is required whenever rituximab therapy is considered.

‘Rituximab-induced inhibition of antiapoptotic cell survival pathways: implications in chemo/immunoresistance, rituximab unresponsiveness, prognostic and novel therapeutic interventions’

“…Further, a subset of responsive patients develops or acquires resistance to further treatment and the mechanism of resistance in this subset is also not clear. There have been some reports suggesting the modulation of CD20 expression and/or circulating CD20 as responsible for unresponsiveness (Haidar et al, 2003;Manshouri et al, 2003;Kennedy et al, 2004). Based on our findings described above, we hypothesized that the development/ acquisition of rituximab resistance may have emanated from perturbations of tumor cells survival signaling pathways and failure of rituximab to alter these pathways.…”

CD20 mutations involving the rituximab epitope are rare in diffuse large B-cell lymphomas and are not a significant cause of R-CHOP failure

“…[20][21][22] Tissue obtained from patients with primary DLBCL at the time of relapse is rare because most patients undergo fine needle aspiration to confirm relapse or have no biopsy. Thus the true incidence of CD20-negative relapses is unknown.…”

Superior Activity of Fusion Protein scFvRit:sFasL over Cotreatment with Rituximab and Fas Agonists

“…Because scFvRit:sFasL directly induces apoptosis, which solely requires the cross-linking of CD20 and Fas, scFvRit:sFasL may be particularly relevant for patients with poor or absent complementdependent cytotoxicity. In addition, treatment with rituximab has been proposed to lead to the development of CD20-negative relapses in some patients, possibly due to tumor cell heterogeneity (25,26). For scFvRit:sFasL, the reciprocal activation of Fas by CD20-immobilized scFvRit:sFasL opens up the possibility to induce apoptosis in neighboring FasL-sensitive leukemic cells that have lost CD20 expression.…”