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Annals of Oncology Advance Access published online on April 11, 2008
Annals of Oncology, doi:10.1093/annonc/mdn163
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Neutrophil role in in vivo anti-lymphoma activity of rituximab: FCGR3B-NA1/NA2 polymorphism does not influence response and survival after rituximab treatment

G. Cartron1,2,*, M. Ohresser1, G. Salles3, P. Solal-Céligny4, P. Colombat5 and H. Watier1

1 EA3853, Immuno-Pharmaco-Génétique des Anticorps Thérapeutiques, Université François Rabelais, Tours
2 INSERM U847, Biothérapies des cellules souches normales et cancéreuses and Service d'Hématologie et Biothérapies, CHU Lapeyronie, Montpellier
3 Service d'Hématologie, Hospices Civiles de Lyon, Université Claude Bernard, Lyon
4 Department of Hématologie, Centre Jean-Bernard, Le Mans
5 Service d'Hématologie et Thérapie Cellulaire, CHU Bretonneau, Tours, France

* Correspondence to: Dr G. Cartron, Service d'Hématologie Clinique, CHU Lapeyronie, 191 avenue du doyen Gaston Giraud 34295 Montpellier, France. Tel: +33 4 67 33 83 62; Fax: +33 4 67 33 91 94; E-mail: guillaume.cartron{at}med.univ-tours.fr

Background: Neutrophils could play an important role in in vivo rituximab anti-lymphoma activity. Fc{gamma}RIIIb is expressed only by neutrophils and Fc{gamma}RIIIb-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, Fc{gamma}RIIIb-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.

Fc{gamma}RIIIb, follicular lymphoma, neutrophils, rituximab

Received for publication January 5, 2008. Revision received February 9, 2008. Accepted for publication March 18, 2008.


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