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.
%0 Journal Article
%1 Ahlgrimm.2011
%A Ahlgrimm, Manfred
%A Pfreundschuh, Michael
%A Kreuz, Markus
%A Regitz, Evi
%A Preuss, Klaus-Dieter
%A Bittenbring, Joerg
%D 2011
%J Blood
%K Aged Aged,_80_and_over Antibodies,_Monoclonal,_Murine-Derived/administration_&_dosage Antineoplastic_Agents/administration_&_dosage Antineoplastic_Combined_Chemotherapy_Protocols/administration_&_dosage Cyclophosphamide/administration_&_dosage Doxorubicin/administration_&_dosage Female Gene_Frequency Humans Lymphoma,_Large_B-Cell,_Diffuse/diagnosis/drug_therapy/genetics/mortality Male Middle_Aged Polymorphism,_Single_Nucleotide/physiology Prednisone/administration_&_dosage Prognosis Randomized_Controlled_Trials_as_Topic Receptors,_IgG/genetics/physiology Survival_Analysis Treatment_Outcome Tumor_Markers,_Biological/analysis/genetics Vincristine/administration_&_dosage
%N 17
%P 4657–4662
%T The impact of Fc-γ receptor polymorphisms in elderly patients with diffuse large B-cell lymphoma treated with CHOP with or without rituximab
%V 118
%X 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.
@article{Ahlgrimm.2011,
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.},
added-at = {2014-10-14T15:27:53.000+0200},
author = {Ahlgrimm, Manfred and Pfreundschuh, Michael and Kreuz, Markus and Regitz, Evi and Preuss, Klaus-Dieter and Bittenbring, Joerg},
biburl = {https://www.bibsonomy.org/bibtex/27363881916ef20a60d9daeabb0bdbae8/drtester},
interhash = {0915d0c8356145a2849f8a3545a8c232},
intrahash = {7363881916ef20a60d9daeabb0bdbae8},
journal = {Blood},
keywords = {Aged Aged,_80_and_over Antibodies,_Monoclonal,_Murine-Derived/administration_&_dosage Antineoplastic_Agents/administration_&_dosage Antineoplastic_Combined_Chemotherapy_Protocols/administration_&_dosage Cyclophosphamide/administration_&_dosage Doxorubicin/administration_&_dosage Female Gene_Frequency Humans Lymphoma,_Large_B-Cell,_Diffuse/diagnosis/drug_therapy/genetics/mortality Male Middle_Aged Polymorphism,_Single_Nucleotide/physiology Prednisone/administration_&_dosage Prognosis Randomized_Controlled_Trials_as_Topic Receptors,_IgG/genetics/physiology Survival_Analysis Treatment_Outcome Tumor_Markers,_Biological/analysis/genetics Vincristine/administration_&_dosage},
number = 17,
pages = {4657–4662},
timestamp = {2014-10-14T15:27:53.000+0200},
title = {The impact of Fc-γ receptor polymorphisms in elderly patients with diffuse large B-cell lymphoma treated with CHOP with or without rituximab},
volume = 118,
year = 2011
}