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

Rituximab binds an epitope on the CD20 antigen, encompassed in exon 5 of the MS4A1 gene. We sequenced this region and correlated the presence of mutations with CD20 protein expression and response to R-CHOP in patients with diffuse large B-cell lymphoma: 264 diagnostic biopsies and 15 biopsies taken at the time of relapse were successfully sequenced. CD20 mutations involving the rituximab epitope were detected in only 1/264 (0.4%) and 1/15 (6%) of the biopsies taken at diagnosis and relapse, respectively. No polymorphic sequence variants were detected in this region. Three patients had malignant cells that were CD20 protein-positive at diagnosis but CD20-negative at relapse. Thus, CD20 mutations involving the rituximab epitope are rare in both de novo and relapsed diffuse large B-cell lymphoma, and do not represent a significant cause of R-CHOP resistance. CD20 protein-negative relapses occur after R-CHOP therapy but their clinical relevance is unknown.