title: Effect of FCGR2A and FCGR3A variants on CLL outcome.
abstract: Polymorphisms of activating Fc-γ receptors (FCGRs) on natural killer cells and macrophages result in variable affinity for immunoglobulin G1 monoclonal antibodies and subsequently modulate antibody-dependent cellular cytotoxicity (ADCC) activity. Whether single-nucleotide polymorphisms of FCGRs correlate with survival of chronic lymphocytic leukemia (CLL) patients treated with a monoclonal antibody containing regimen is unclear. We assessed the FCGR3A and FCGR2A genotype of patients enrolled in the REACH trial, where patients received fludarabine and cyclophosphamide (FC) or rituximab plus FC (R-FC). FCGR3A and FCGR2A polymorphisms did not demonstrate prognostic significance in the FC arm (P = .42 and P = .64, respectively) or R-FC arm (P = .41 and P = .88, respectively) with respect to progression free survival. Patients with intermediate affinity genotypes (FV and HR) benefited significantly from addition of rituximab (hazard ratio = 0.55 [0.37-0.8 CI]; P = .0017 and hazard ratio = 0.63 [0.44-0.9 CI]; P = .011, respectively). Similar benefit was suggested for patients with high- affinity VV and HH (hazard ratio = 0.86 [0.4-1.84 CI]; P = .7 and hazard ratio = 0.7 [0.41-1.18 CI]; P = .18, respectively) and low-affinity FF and RR (hazard ratio = 0.85 [0.56-1.29 CI]; P = .44 and hazard ratio = 0.82 [0.47-1.42 CI]; P = .48, respectively). Overall, our results suggest that FCGR2A and FCGR3A polymorphisms do not significantly influence the outcomes of relapsed or refractory CLL patients treated with FC or the monoclonal antibody regimen R-FC.
authors: Molecular Diagnostics and Cancer Cell Biology, Genentech Inc, South San Francisco, CA, USA. dornan.david@gene.com
authors: David
authors: D
authors: Dornan
authors: Olivia
authors: O
authors: Spleiss
authors: Ru-Fang
authors: RF
authors: Yeh
authors: Guillemette
authors: G
authors: Duchateau-Nguyen
authors: Annika
authors: A
authors: Dufour
authors: Jianguo
authors: J
authors: Zhi
authors: Tadeusz
authors: T
authors: Robak
authors: Sergey I
authors: SI
authors: Moiseev
authors: Anna
authors: A
authors: Dmoszynska
authors: Philippe
authors: P
authors: Solal-Celigny
authors: Krzysztof
authors: K
authors: Warzocha
authors: Javier
authors: J
authors: Loscertales
authors: John
authors: J
authors: Catalano
authors: Boris V
authors: BV
authors: Afanasiev
authors: Loree
authors: L
authors: Larratt
authors: Viktor A
authors: VA
authors: Rossiev
authors: Isabelle
authors: I
authors: Bence-Bruckler
authors: Christian H
authors: CH
authors: Geisler
authors: Marco
authors: M
authors: Montillo
authors: Michael K
authors: MK
authors: Wenger
authors: Martin
authors: M
authors: Weisser
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000493:pharmacokinetics / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D017452:Receptors, IgG / Q000235:genetics*; D000069283:Rituximab; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C445323:FCGR2A protein, human; C496124:FCGR3A protein, human; D017452:Receptors, IgG; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine