Fcgamma receptor IIIA polymorphisms and efficacy of rituximab therapy on Chinese diffuse large B-cell lymphoma

Rituximab is used extensively in combination with chemotherapy to cure non-Hodgkin's lymphoma (NHL), and not only accelerates short-term improvement, but also prolongs patient survival and decreases receptor relapse. The aim of this study was to evaluate the impact of Fcgamma IIIA (FcgammaRIIIA) gene polymorphisms on the response to rituximab therapy for newly diagnosed B-cell lymphomas.

Patients with newly diagnosed histologically-proven CD20-positive B-cell lymphoma were eligible for the study. All of the patients received rituximab combined with chemotherapy (CHOP). The FcgammaRIIIA type was analyzed by PCR. The initial efficacy was assessed after 6 cycles and the long-term survival was determined.

Thirty-four patients were recruited between October 2005 and April 2006. The FcgammaRIIIA distribution was as follows: 11 patients were VV, 5 were FF, and 18 were VF. After a median of 6 cycles (range 4-8) of rituximab combined chemotherapy, the overall response rate was 79% (82% in the VV group, 83% in the VF group, and 60% in the FF group; P=0.04). After a median follow-up time of 37 months (range 34-41), there were 12 relapses among 27 responders (44%); 5 of 9 patients (5/9) in the VV group, 5 of 15 patients (33%) in the VF group, and 2 of 3 patients (2/3) in the FF group (P=0.21). The 1-year overall survival in the VV, FF, and VF groups was 80%, 60%, and 80%, respectively, and the 3-year overall survival was 58%, 40%, and 69%, respectively (P=0.08). After analysis by COX regression, only the international prognosis index and response to initial treatment were significantly related to overall survival.

The distribution of FcgammaRIIIA polymorphisms in this B-cell lymphoma population shows that VF is most frequently expressed, followed by VV and FF. Patients with the FcgammaRIIIA VV and VF types are more sensitive to the initial treatment of rituximab combined with chemotherapy and have superior long-term survival compared with those with FF. Nevertheless, FcgammaRIIIA polymorphisms do not predict prognosis independently.