title: Fc gamma RIIIa and Fc gamma RIIa polymorphisms do not predict response to rituximab in B-cell chronic lymphocytic leukemia.
abstract: In follicular lymphoma (FL), genomic polymorphisms corresponding to the expression of valine (V) or phenylalanine (F) at amino acid 158 of Fc gamma RIIIa alter the binding affinity of immunoglobulin G1 (IgG1) to the receptor and have been associated with varied responses to rituximab. We examined Fc gamma RIIIa polymorphisms of 30 CLL patients with the phenotypes V/V (n = 6), V/F (n = 12), and F/F (n = 12) treated with thrice-weekly rituximab (375 mg/m(2)) for 4 weeks to correlate polymorphism type with infusion toxicity and response. Infusion toxicity (grade 3 or greater or hypoxia/hypotension requiring transient cessation of therapy) was observed equally among the groups (V/V, 50%; V/F, 33%; F/F, 41.6%; P =.78). The response to rituximab was also similar among the different polymorphism phenotypes (V/V, 33%; V/F, 41.6%; F/F, 50%). These data suggest that Fc gamma RIIIa polymorphisms are not predictive of response in CLL and that, unlike the case with FL, mechanisms of tumor clearance other than antibody-dependent cellular cytotoxicity may be more important.
authors.affiliation: Division of Hematology-Oncology and the Department of Biostatistics, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Sherif S
authors.initials: SS
authors.lastname: Farag
authors.forename: Ian W
authors.initials: IW
authors.lastname: Flinn
authors.forename: Rama
authors.initials: R
authors.lastname: Modali
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Lehman
authors.forename: Donn
authors.initials: D
authors.lastname: Young
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D017452:Receptors, IgG / Q000235:genetics*; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; D000970:Antineoplastic Agents; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG; D000069283:Rituximab