TY - JOUR
T1 - Fc gamma receptor 3A and 2A polymorphisms do not predict response to rituximab in follicular lymphoma
AU - Kenkre, Vaishalee P.
AU - Hong, Fangxin
AU - Cerhan, James R.
AU - Lewis, Marcia
AU - Sullivan, Leslie
AU - Williams, Michael E.
AU - Gascoyne, Randy D.
AU - Horning, Sandra J.
AU - Kahl, Brad S.
N1 - Publisher Copyright:
© 2016 American Association for Cancer Research.
PY - 2016/2/15
Y1 - 2016/2/15
N2 - Purpose: Preclinical studies suggest that SNPs in the Fc gamma receptor (FCGR) genes influence response to rituximab, but the clinical relevance of this is uncertain. Experimental Design: 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 retreatment (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-naive, low tumor burden FL, we conclude that the FCGR3A and FCGR2A SNPs do not confer differential responsiveness to rituximab.
AB - Purpose: Preclinical studies suggest that SNPs in the Fc gamma receptor (FCGR) genes influence response to rituximab, but the clinical relevance of this is uncertain. Experimental Design: 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 retreatment (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-naive, low tumor burden FL, we conclude that the FCGR3A and FCGR2A SNPs do not confer differential responsiveness to rituximab.
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U2 - 10.1158/1078-0432.CCR-15-1848
DO - 10.1158/1078-0432.CCR-15-1848
M3 - Article
C2 - 26510856
AN - SCOPUS:84964222917
SN - 1078-0432
VL - 22
SP - 821
EP - 826
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 4
ER -