FCGR3A gene polymorphisms may correlate with response to frontline R-CHOP therapy for diffuse large B-cell lymphoma

• Published in: Blood Vol. 108; no. 8; pp. 2720 - 2725
• Main Authors: Kim, Dong Hwan, Jung, Hee Du, Kim, Jong Gwang, Lee, Je-Jung, Yang, Deok-Hwan, Park, Yeon Hee, Do, Young Rok, Shin, Ho Jin, Kim, Min Kyoung, Hyun, Myung Soo, Sohn, Sang Kyun
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.10.2006; The Americain Society of Hematology
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Alleles; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Base Sequence; Biological and medical sciences; Combined Modality Therapy; Cyclophosphamide - administration & dosage; DNA, Neoplasm - genetics; Doxorubicin - administration & dosage; Female; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, B-Cell - drug therapy; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - immunology; Lymphoma, B-Cell - therapy; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - immunology; Lymphoma, Large B-Cell, Diffuse - therapy; Male; Medical sciences; Middle Aged; Polymorphism, Single Nucleotide; Prednisone - administration & dosage; Receptors, IgG - genetics; Retrospective Studies; Rituximab; Vincristine - administration & dosage; Antineoplastic agent; Human; Drug combination; Treatment resistance; Treatment; Genetic variability; Diffuse large cell lymphoma; CHOP regimen; Genotype; B cell neoplasm; Lymphoid neoplasm; Therapeutic protocol
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-01-009480

The precise mechanism of rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP) therapy in diffuse large B-cell lymphoma (DLBCL) is not fully elucidated. Besides overcoming bcl-2-mediated chemoresistance, antibody-dependent cellular cytotoxicity (ADCC), which is activated by effector cells via immunoglobulin G (IgG) fragment C receptors (FcRs), was also proposed as a mechanism of rituximab. The current study evaluated the impact of FcR polymorphism on the response to R-CHOP therapy for DLBCL with the basis that FcR polymorphism can affect rituximab's affinity for ADCC effector cells. The FCGR3A and FCGR2A gene polymorphisms were determined in DLBCL patients receiving R-CHOP (n = 113) compared with CHOP therapy (n = 85). The FCGR3A valine (V) allele was significantly correlated with a higher complete response rate to R-CHOP compared with the phenylalanine (F) allele (88% in V/V vs 79% in V/F vs 50% in F/F; P = .002), while no difference was found between FCGR2A polymorphisms. In addition, V/V allele was associated with faster achievement of response than other alleles. The impact of the FCGR3A gene polymorphism on response rate was not noted in the CHOP group. In terms of overall or event-free survival, no difference was found according to FCGR3A or FCGR2A alleles. The FCGR3A single nucleotide polymorphism (SNP) is predictive of response to R-CHOP, but does not correlate with survival in patients with DLBCL.