The impact of Fc-γ receptor polymorphisms in elderly patients with diffuse large B-cell lymphoma treated with CHOP with or without rituximab

• Published in: Blood Vol. 118; no. 17; pp. 4657 - 4662
• Main Authors: Ahlgrimm, Manfred, Pfreundschuh, Michael, Kreuz, Markus, Regitz, Evi, Preuss, Klaus-Dieter, Bittenbring, Joerg
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 27.10.2011; Americain Society of Hematology; American Society of Hematology
• Subjects: Aged; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived - administration & dosage; Antineoplastic Agents - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Biological and medical sciences; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Cyclophosphamide - administration & dosage; Doxorubicin - administration & dosage; Female; Gene Frequency; Hematologic and hematopoietic diseases; Humans; Immunobiology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoid Neoplasia; Lymphoma, Large B-Cell, Diffuse - diagnosis; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - mortality; Male; Medical sciences; Middle Aged; Polymorphism, Single Nucleotide - physiology; Prednisone - administration & dosage; Prognosis; Randomized Controlled Trials as Topic; Receptors, IgG - genetics; Receptors, IgG - physiology; Rituximab; Survival Analysis; Treatment Outcome; Vincristine - administration & dosage; Human; Antineoplastic agent; Drug combination; Genetic variability; Hematology; Rituximab; Genotype; B cell neoplasm; Malignant hemopathy; Monoclonal antibody; FcγR receptor; Non Hodgkin lymphoma; Treatment; Lymphoproliferative syndrome; Immunotherapy; Diffuse large B cell lymphoma; Therapeutic protocol; Elderly; Cancer; Polymorphism
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2011-04-346411

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.