1. Neutrophil role in in vivo anti-lymphoma activity of rituximab: FCGR3B-NA1/NA2 polymorphism does not influence response and survival after rituximab treatment
- Author
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Philippe Colombat, Marc Ohresser, Philippe Solal-Celigny, Gilles Salles, Hervé Watier, Guillaume Cartron, Dequeant, Evelyne, Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Institut de recherche en biothérapie (IRB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Génétique, immunothérapie, chimie et cancer (GICC), UMR 6239 CNRS [2008-2011] (GICC UMR 6239 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), and Université de Tours-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Male ,Neutrophils ,[SDV]Life Sciences [q-bio] ,Follicular lymphoma ,Antineoplastic Agents ,GPI-Linked Proteins ,Antibodies, Monoclonal, Murine-Derived ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,In vivo ,hemic and lymphatic diseases ,medicine ,Humans ,Lymphoma, Follicular ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,0303 health sciences ,Polymorphism, Genetic ,biology ,business.industry ,Receptors, IgG ,Antibodies, Monoclonal ,Hematology ,Gene rearrangement ,medicine.disease ,3. Good health ,Lymphoma ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,Oncology ,Monoclonal ,Immunology ,biology.protein ,Female ,Rituximab ,Bone marrow ,Antibody ,business ,030215 immunology ,medicine.drug - Abstract
Background Neutrophils could play an important role in in vivo rituximab anti-lymphoma activity. FcγRIIIb is expressed only by neutrophils and FcγRIIIb-neutrophil antigen (NA)1/NA2 polymorphism influenced phagocytosis of immunoglobulin G1-opsonized particles. We formulated the hypothesis that if neutrophils are critical cells for in vivo rituximab activity, FcγRIIIb-NA1/NA2 polymorphism could influence the response to rituximab. Patients and methods FCGR3B-NA1/NA2 genotypes were determined in 46 patients having received rituximab for a previously untreated, follicular, non-Hodgkin's lymphoma. The clinical response and the disappearance of the BCL2-JH gene rearrangement in both peripheral blood and bone marrow were evaluated at 2 months (M2) and each year during 7 years. Results : They were 13% homozygous for FCGR3B-NA1, 61% homozygous for FCGR3B-NA1/NA2 and 26% heterozygous. The objective response rates at M2 were 67% in homozygous FCGR3B-NA1 patients compared with 75% in homozygous FCGR3B-NA2 and 75% in heterozygous patients (not significant). We found no difference for progression-free and overall survival by FCGR3B-NA1/NA2 genotypes. Conclusion : These results indicate no association between FCGR3B-NA1/NA2 polymorphism and response to rituximab indicating no significant role of phagocytosis mediated by neutrophils in in vivo mechanism of rituximab activity.
- Published
- 2008