Homozygous FCGR3A‐158V alleles predispose to late onset neutropenia after CHOP‐R for diffuse large B‐cell lymphoma
Recent reports suggest genetic polymorphisms influence susceptibility to rituximab‐induced late‐onset neutropenia (LON),
which in turn may be a predictor of good outcome in B‐cell lymphoma. Aims
We report the largest study to date assessing FCGR3A‐V158F
polymorphisms in diffuse large B‐cell lymphoma (DLBCL) treated with cyclophosphamide/hydroxydaunorubicin/Oncovin (vincristine)/prednisone/rituximab (CHOP‐R). The influence
of C1qA‐A276G polymorphisms in DLBCL, and the impact of both polymorphisms on susceptibility to LON and outcome were also examined.
115 DLBCL patients treated with CHOP‐R were compared with 105 healthy White people controls with regards to FCGR3A‐V158F
and C1qA‐A276G polymorphisms. LON incidence and event‐free and overall survival (EFS and OS) were analysed for linkage to either polymorphism.
The FCGR3A‐V158F but not the C1qA‐A276G polymorphism influenced the risk of developing
LON. 50% of FCGR3A‐158V/V patients experienced LON. In contrast, only 7% V/F and 2% F/F
experienced LON. The FCGR3A‐158V/V genotype was associated with LON compared with V/F (P = 0.028)
and F/F genotypes (P = 0.005). Although no patients with either LON or FCGR3A‐158V homozygosity relapsed compared with 33% FCGR3A‐158F/F
and 21% non‐LON, this did not translate into improved EFS or OS. Conclusions
Polymorphic analysis may be a predictive
tool to identify those at high risk of LON. Prospective studies are required to establish definitively if LON or FCGR3A‐158V/V genotype influences outcome.