Frequently Asked Questions

What is PGxPredict™:RITUXIMAB test?
The PGxPredict:RITUXIMAB test is a pharmacogenetic test that will provide information on whether a patient is more likely to respond to rituximab monotherapy. Rituximab is an immunotherapeutic agent of the IgG1 subclass. This test genotypes a single nucleotide polymorphism (SNP; rs396991, 4985GT) in the FCGR3A gene that encodes the Fc gamma IIIa receptor to which rituximab binds. This SNP results in an amino acid change at position 158 where valine (V) is replaced with phenylalanine (F). This amino acid change has been shown to affect the binding affinity of IgG1 antibodies, including rituximab, to the receptor.¹ In two independent studies, this SNP has been shown to be associated with better response to rituximab monotherapy in the treatment of follicular, CD20-positive, B-cell NHL. ^2,3

What is FCGR3A?
FCGR3A is the gene that encodes the Fc gamma IIIa receptor to which rituximab binds. Rituximab binds with greater affinity to the 158Val/Val variant of the receptor compared to the 158Val/Phe or 158Phe/Phe forms.¹ In addition, patients with two copies of the Val allele have been shown to have an increased likelihood of response to rituximab monotherapy.^2,3

How do I interpret the results of my patient’s test?
The results of the test will be presented in the report as More Likely or Not More Likely to Respond based on the following table:

*SNP 4985GT is rs396991

What is the likelihood that my patient will be categorized as More Likely to Respond?
Approximately, 20% of patients will have the Val/Val genotype of the receptor, assigning them to the More Likely to Respond group.  Some patients who do not have the 158ValVal genotype may still respond to rituximab treatment: twelve months after rituximab monotherapy 27% and 52% of Phe-carrier patients (158Val/Phe or 158Phe/Phe genotypes) were responsive to rituximab in the studies by Weng and Levy (2003) and Cartron et al (2002), respectively. However, as shown in the summary table below, patients of the 158Val/Val genotype of the receptor are significantly more likely to be responders at all time points than Phe-carriers.

How is the test conducted?
A test kit is sent to the provider and the test can be administered in the provider’s office. Whole blood is collected via fingerstick onto sample collection cards, which are shipped to PGxHealth for analysis. DNA is extracted from the blood sample, and analyzed for the patient’s genotype using a Restriction Length Fragment Polymorphism (RFLP) method using the HincII enzyme.

Who should be tested?
Patients being considered for treatment of follicular, CD20-positive NHL may be considered for testing.

How long will it take to get the results?
Results will be available within two to five days of sample receipt. Test results will be sent to the ordering physician.

How can I order a test?
Please note that only healthcare providers can order this test. Physicians can order the test by calling:
1-877-4-RITUXIMAB (1-877-474-8894) or by emailing rituximabtestinfo@pgxhealth.com.

Is the test covered by my patient’s health insurance?
PGxHealth provides a service to help determine if insurance carriers will cover all or a portion of the cost of the test. PGxHealth will make every effort to collect payment from your patient’s insurance company. It is important to remember that the patient is ultimately responsible for the entire cost of the test.

Who will have access to my patient’s test results?
Only the ordering physician or those designated by the patient will be sent test results. The insurance carrier may also require results if the patient has requested that PGxHealth bill them for the cost of the test. No one else will be sent the results unless written authorization is given to PGxHealth by the patient.

References

1. Dall’Ozzo S, Tartas S, Paintaud G, Cartron G, Colombat P, Bardos P, Watier H, and Thibault G. 2004. Rituximab-dependent cytotoxicity by natural killer cells: Influence of FCGR3A polymorphism on concentration-effect relationship. Cancer Research, 64:4664-4669.

2. Cartron G, Dacheux L, Salles G, Solal-Celigny P, Bardos P, Colombat P and Watier H. 2002. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgRIIIa gene. Blood, 99: 754-758.

3. Weng W-K and Levy R. 2003. Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. Journal of Clinical Oncology, 21(21): 3940-3947.

1-877-2-PGXHEALTH (877-274-9432)