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

• Published in: Haematologica (Roma) Vol. 94; no. 3; pp. 423 - 427
• Main Authors: JOHNSON, Nathalie A, LEACH, Stephen, WOOLCOCK, Bruce, DELEEUW, Ronald J, BASHASHATI, All, SEHN, Laurie H, CONNORS, Joseph M, CHHANABHAI, Mukesh, BROOKS-WILSON, Angela, GASCOYNE, Randy D
• Format: Journal Article
• Language: English
• Published: Pavia Ferrata Storti Foundation 01.03.2009
• Subjects: Amino Acid Sequence; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - metabolism; Antibodies, Monoclonal, Murine-Derived; Antigens, CD20 - genetics; Antigens, CD20 - metabolism; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Binding Sites, Antibody - genetics; Biological and medical sciences; Cyclophosphamide - administration & dosage; DNA Mutational Analysis; Doxorubicin - administration & dosage; Drug Resistance, Neoplasm - genetics; Epitopes - genetics; Female; Hematologic and hematopoietic diseases; Humans; Immunohistochemistry; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - metabolism; Male; Malignant Lymphomas; Medical sciences; Middle Aged; Molecular Sequence Data; Mutation; Neoplasm Recurrence, Local; Prednisone - administration & dosage; Rituximab; Vincristine - administration & dosage; Antineoplastic agent; Drug combination; DLBCL; Antigenic determinant; Hematology; R-CHOP; Rituximab; B cell neoplasm; Malignant hemopathy; Monoclonal antibody; Treatment; Diffuse large cell lymphoma; Lymphoproliferative syndrome; Immunotherapy; CD20 antigen; Genetics; Diffuse large B cell lymphoma; Mutation; Cancer
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2008.001024

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.