Immunoglobulin G Fc Receptor Polymorphisms and Clinical Course in Follicular Lymphoma Patients.

Patients with low-grade B cell lymphoma, such as follicular lymphoma usually have an indolent clinical course. In most of the cases, patients do not require therapy at the time of diagnosis. Instead, patients can be monitored from months to years before the need for therapy. However, the time interval from diagnosis to the first therapy in these patients can vary significantly. In addition, the overall clinical course is heterogeneous in these patients with variable length of survival after diagnosis. The pathobiological basis of this hetergenisity is not known. We have recently found that IgG Fc receptor (FcγR) polymorphisms correlated with clinical outcome after immunotherapies in patients with follicular lymphoma. In one case, FcγRIIIa 158 V/F and FcγRIIa 131 H/R polymorphisms predicted the response to anti-CD20 antibody, rituximab therapy probably due to their role in the antibody-dependent cellular cytotoxicity. One question is whether the FcγR polymorphisms are correlated with the general clinical course of follicular lymphoma due toq their role in innate immunity. We therefore tested if FcγRIIIa 158 V/F, FcγRIIa 131 H/R and FcγRIIb 232 I/T polymorphisms predict clinical course of a group of 307 patients with follicular lymphoma. None of the three FcγR polymorphisms tested correlated with the time interval from diagnosis to first therapy, or with overall survival in this group of patients. We then tested whether FcγR polymorphisms have predictive value on clinical response to chemotherapy. Of 307 patients, only 158 patients received chemotherapy alone as first therapy, while the rest of the patients have received additional idiotype vaccination or rituximab. In the analysis of these 158 patients, there was no correlation between the FcγR polymorphisms and response rate to chemotherapy or time to progression after chemotherapy. Our results did not find any association between the three FcγR polymorphisms tested and clinical course of disease or response to chemotherapy in patients with follicular lymphoma, suggesting that the predictive value of FcγR polymorphisms on the clinical responses to rituximab is specific to the monoclonal antibody therapy.