title: The impact of Fc-γ receptor polymorphisms in elderly patients with diffuse large B-cell lymphoma treated with CHOP with or without rituximab.
abstract: Fcγ receptor (FcγR) polymorphisms have been shown to affect rituximab-mediated antibody-dependent cellular cytotoxicity. Of 512 patients with diffuse large B-cell lymphoma treated in the RICOVER-60 trial, carriers of FcγRIII 158 valine homozygous receptors (V/V) presented with a slightly decreased incidence of B-symptoms (158 V/V: 26%, V/F: 35%, phenylalanine receptors [F/F]: 42%; P = .037). Survival curves of all FcγR single nucleotide polymorphisms were superimposable after cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); but after CHOP with rituximab (R-CHOP), event-free survival (EFS) and progression-free survival (PFS), but not overall survival, of FcγRIIIa 158 F/F had a trend to be lower than those of 158 V/F and 158 V/V: 3-year EFS: FcγRIIIa 158 F/F: 64.5%, 158 V/F: 70.2%, 158 V/V: 76.9% (log-rank test: P = .224 F/F vs V/V; P = .285 F/F vs V/F + V/V); 3-year PFS: FcγRIIIa 158 F/F: 68.3%, V/F: 76.1%, V/V: 80.5% (log-rank test: P = .233 for F/F vs V/V; P = .185 for F/F vs V/F + V/V). By multivariate analysis adjusting for International Prognostic Index factors, relative risk of F/F compared with V/F plus V/V was 1.80 (P = .052) for PFS and 1.55 (P = .120) for EFS. The interaction of R-CHOP, but not CHOP with FcγRIIIa polymorphisms, indicates a window of opportunity for CD20 antibodies designed to mediate enhanced antibody-dependent cellular cytotoxicity.
authors: Saarland University Medical School, Homburg, Germany.
authors: Manfred
authors: M
authors: Ahlgrimm
authors: Michael
authors: M
authors: Pfreundschuh
authors: Markus
authors: M
authors: Kreuz
authors: Evi
authors: E
authors: Regitz
authors: Klaus-Dieter
authors: KD
authors: Preuss
authors: Joerg
authors: J
authors: Bittenbring
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005787:Gene Frequency; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011241:Prednisone / Q000008:administration & dosage; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D017452:Receptors, IgG / Q000235:genetics* / Q000502:physiology; D000069283:Rituximab; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C496124:FCGR3A protein, human; D017452:Receptors, IgG; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone