FCGR3A gene polymorphisms may correlate with response to frontline R-CHOP therapy for diffuse large B-cell lymphoma.
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.
Kim
Dong Hwan
DH
Department of Hematology/Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Ilwon-dong 50, Kangnam-gu, Seoul, Korea 135-710. drkiim@medimail.co.kr
Jung
Hee Du
HD
Kim
Jong Gwang
JG
Lee
Je-Jung
JJ
Yang
Deok-Hwan
DH
Park
Yeon Hee
YH
Do
Young Rok
YR
Shin
Ho Jin
HJ
Kim
Min Kyoung
MK
Hyun
Myung Soo
MS
Sohn
Sang Kyun
SK
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001483:Base Sequence; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004273:DNA, Neoplasm / Q000235:genetics; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011241:Prednisone / Q000008:administration & dosage; D017452:Receptors, IgG / Q000235:genetics*; D012189:Retrospective Studies; D000069283:Rituximab; D014750:Vincristine / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D004273:DNA, Neoplasm; C445323:FCGR2A protein, human; C496124:FCGR3A protein, human; D017452:Receptors, IgG; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone