TransPredict: FCGR3A 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 TransPredict:FCGR3ATest
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 TransPredict:FCGR3Atest will identify a subset (~20%) of patients
who may be more likely to respond to rituximab monotherapy.
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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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