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Effect of FCGR2A and FCGR3A variants on CLL outcome.
- Source :
-
Blood [Blood] 2010 Nov 18; Vol. 116 (20), pp. 4212-22. Date of Electronic Publication: 2010 Aug 12. - Publication Year :
- 2010
-
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.
- Subjects :
- Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Murine-Derived pharmacokinetics
Antibodies, Monoclonal, Murine-Derived therapeutic use
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Cyclophosphamide therapeutic use
Disease-Free Survival
Female
Genotype
Humans
Leukemia, Lymphocytic, Chronic, B-Cell diagnosis
Leukemia, Lymphocytic, Chronic, B-Cell genetics
Male
Middle Aged
Prognosis
Rituximab
Treatment Outcome
Vidarabine analogs & derivatives
Vidarabine therapeutic use
Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
Polymorphism, Single Nucleotide genetics
Receptors, IgG genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 116
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 20705761
- Full Text :
- https://doi.org/10.1182/blood-2010-03-272765