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The PGxPredict:RITUXIMAB Test:
Helping Individualize Treatment for Follicular Non-Hodgkin’s Lymphoma Patients
Rituximab Triggers B-Cell Lysis via Antibody-Dependent Cellular Cytotoxicity
- Antibody-dependent cellular cytotoxicity (ADCC) is an important mechanism for rituximab efficacy1
- The fragment antigen binding portion of rituximab binds to the target protein, CD20, on B cells. The Fc fragment engages Fc gamma 3A receptors (FCGR3A) on natural killer (NK) cells.
FCGR3A Genotype Impacts the Binding Affinity of Rituximab for Natural Killer Cells
- The FCGR3A gene is polymorphic at position 4985 where there may either be a guanine (G) or thymine (T) nucleotide.
- The 4985G>T polymorphism changes the coding for the receptor protein by replacing a phenylalanine (F) at amino acid 158 with a valine (V), denoted F158V.
- The V and F isoforms of the receptor have different binding affinities for rituximab.2
- The V isoform promotes more efficient tumor cell lysis in vitro.2
FCGR3A Genotype is Predictive of Rituximab Binding Affinity to NK Cells
Follicular Lymphoma Patients Homozygous for the 158V Isoform of FCGR3A Achieve Higher Response Rates With Rituximab Monotherapy
- Two independent studies of follicular lymphoma patients receiving rituximab monotherapy confirmed that patients who are homozygous for the 158V isoform of FCGR3A achieve significantly higher response rates than patients who are heterogeneous or homozygous for the 158F isoform of FCGR3A.3,4
The PGxPredict:RITUXIMAB Test Can Help Identify Follicular Lymphoma Patients Who May Experience a Higher Level of Response to Rituximab Monotherapy
| Nucleotide Change |
Amino Acid Change |
Effect on Response to Rituximab Monotherapy |
| 4985 G/G |
158 V/V |
High Probability of Response |
| 4985 G/T |
158 F/V |
Average Probability of Response |
| 4985 T/T |
158 F/F |
Average Probability of Response |
- The PGxPredict:RITUXIMAB test will identify a subset (~20%) of patients who may be more likely to respond to rituximab monotherapy.
Click here to download the PGxPredict:RITUXIMAB brochure
References
1. http://www.rituxan.com/lymphoma/hcp/MOA/index.m. Accessed April 13, 2009.
2. Dall’Ozzo S, et al. Cancer Research, 2004; 64:4664-4669.
3. Cartron G, et al, Blood. 2002; 99(3):754-758.
4. Weng W-K and Levy R. Journal of Clinical Oncology, 2003; 21(21):3940-3947.
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