FC-gamma receptor IIIA (FCGR3A) polymorphism and DFS in follicular lymphoma patients after idiotype vaccination in first remission.

Abstract

e13125 Background: FCGR3A (CD16) polymorphisms affect the affinity of macrophages and NK cells to bind IgG1 and thus mediate ADCC. The FCGR3A-158-V allotype is reportedly associated with better response rates after rituximab therapy and longer progression-free survival after idiotype (Id) vaccination as compared to the 158-F allotype in follicular lymphoma patients (FL). We previously reported prolonged disease-free survival (DFS) in patients receiving vaccination with autologous tumor-derived Id conjugated to keyhole limpet hemocyanin (KLH) administered with GM-CSF as compared to patients receiving KLH control with GM-CSF. However, the underlying mechanism of the antitumor effect remains unknown. Methods: The objective of this study was to evaluate the prognostic significance of FCGR3A polymorphisms resulting in an amino acid substitution at position 158 in FL patients from the randomized, double-blind BV301trial who received active Id-KLH (N=75) or KLH control (N= 41) vaccine after achieving complete remission or complete remission unconfirmed with PACE chemotherapy. The primary endpoint of this study was DFS from randomization after chemotherapy response assessment. Results: The genotype distribution included 44% F/F, 48% F/V, 8% V/V in the Id-KLH arm, and 44% F/F, 41% F/V, 15% V/V in the KLH arm. There were no statistically significant differences in demographics, clinical and histologic features, and number of PACE cycles received among the 3 genotype groups or between study arms. Median DFS estimates by 3 genotype groups within the Id-KLH arm were not significantly different (38.5 mo F/F, 46.0 mo V/F, 40.2 mo V/V, p= 0.543). Median DFS estimates between the V carriers (V/V and F/V) and F/F genotypes within the Id-KLH arm were not significantly different (44.2 mo vs. 38.5 mo, p=0.448). Comparisons between the Id- KLH and KLH arm suggest a trend toward better DFS in the Id-KLH arm in all V carriers (44.2 vs. 26.2mo, p= 0.069) but not in F/F genotypes. Conclusions: Our results suggest that polymorphisms in FCGR3A do not have prognostic value in FL patients treated with Id-KLH vaccination. However, our small sample size may preclude the identification of significant results. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biovest International, Inc. Biovest International, Inc. Biovest International, Inc.