Neutrophil role in in vivo anti-lymphoma activity of rituximab: FCGR3B-NA1/NA2 polymorphism does not influence response and survival after rituximab treatment.
BACKGROUND
Neutrophils could play an important role in in vivo rituximab anti-lymphoma activity. FcgammaRIIIb is expressed only by neutrophils and FcgammaRIIIb-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, FcgammaRIIIb-NA1/NA2 polymorphism could influence the response to rituximab.


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.


CONCLUSIONS
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.
Cartron
G
G
EA3853, Immuno-Pharmaco-Génétique des Anticorps Thérapeutiques, Université François Rabelais, Tours; INSERM U847, Biothérapies des cellules souches normales et cancéreuses and Service d'Hématologie et Biothérapies, CHU Lapeyronie, Montpellier. Electronic address: guillaume.cartron@med.univ-tours.fr.
Ohresser
M
M
EA3853, Immuno-Pharmaco-Génétique des Anticorps Thérapeutiques, Université François Rabelais, Tours.
Salles
G
G
Service d'Hématologie, Hospices Civiles de Lyon, Université Claude Bernard, Lyon.
Solal-Céligny
P
P
Department of Hématologie, Centre Jean-Bernard, Le Mans.
Colombat
P
P
Service d'Hématologie et Thérapie Cellulaire, CHU Bretonneau, Tours, France.
Watier
H
H
EA3853, Immuno-Pharmaco-Génétique des Anticorps Thérapeutiques, Université François Rabelais, Tours.
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics* / Q000276:immunology; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG; D000069283:Rituximab