Fc Gamma Receptor 3A and 2A Polymorphisms Do Not Predict Response to Rituximab in Follicular Lymphoma.
OBJECTIVE
Preclinical studies suggest that SNPs in the Fc gamma receptor (FCGR) genes influence response to rituximab, but the clinical relevance of this is uncertain.


METHODS
We prospectively obtained specimens for genotyping in the rituximab extended schedule or re-treatment trial (RESORT) study, in which 408 previously untreated, low tumor burden follicular lymphoma (FL) patients were treated with single agent rituximab. Patients received rituximab in 4 weekly doses and responders were randomized to rituximab re-treatment (RR) upon progression versus maintenance rituximab (MR). SNP genotyping was performed in 321 consenting patients.


RESULTS
Response rates to initial therapy and response duration were correlated with the FCGR3A SNP at position 158 (rs396991) and the FCGR2A SNP at position 131 (rs1801274). The response rate to initial rituximab was 71%. No FCGR genotypes or grouping of genotypes were predictive of initial response. A total of 289 patients were randomized to RR (n = 143) or to MR (n = 146). With a median follow-up of 5.5 years, the 3-year response duration in the RR arm and the MR arm was 50% and 78%, respectively. Genotyping was available in 235 of 289 randomized patients. In patients receiving RR (n = 115) or MR (n = 120), response duration was not associated with any FCGR genotypes or genotype combinations.


CONCLUSIONS
Based on this analysis of treatment-naïve, low tumor burden FL, we conclude that the FCGR3A and FCGR2A SNPs do not confer differential responsiveness to rituximab.
Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
Vaishalee P
VP
Kenkre
Department of Biostatistics and Computational Biology, Harvard School of Public Health, Dana Farber Cancer Institute, Boston, Massachusetts.
Fangxin
F
Hong
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
James R
JR
Cerhan
Transgenomic, Inc., Omaha, Nebraska.
Marcia
M
Lewis
Transgenomic, Inc., Omaha, Nebraska.
Leslie
L
Sullivan
Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia.
Michael E
ME
Williams
Department of Pathology, British Columbia Cancer Agency and Center for Lymphoid Cancer, Vancouver, BC, Canada.
Randy D
RD
Gascoyne
Genentech/Roche, Inc., South San Francisco, California.
Sandra J
SJ
Horning
Washington University School of Medicine, St. Louis, Missouri. bkahl@dom.wustl.edu.
Brad S
BS
Kahl
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D020641:Polymorphism, Single Nucleotide; D016032:Randomized Controlled Trials as Topic; D017452:Receptors, IgG / Q000235:genetics*; D000069283:Rituximab / Q000494:pharmacology / Q000627:therapeutic use*; D017422:Sequence Analysis, DNA
D000970:Antineoplastic Agents; C445323:FCGR2A protein, human; C496124:FCGR3A protein, human; D017452:Receptors, IgG; D000069283:Rituximab