Polymorphisms in FcγRIIIA (CD16) receptor expression are associated with clinical response to rituximab in Waldenstrom's macroglobulinemia.

6556 Background: Polymorphisms in FcγRIIIA (CD16) receptor expression modulate human IgG1 binding, and antibody dependent cell mediated cytotoxicity, and may therefore impact responses to rituximab in patients with WM. METHODS We therefore performed sequencing of all DNA coding regions for FcγRIIIA in 58 patients with Waldenstrom's macroglobulinemia (WM) treated with rituximab. Two distinct, but linked polymorphisms (FcγRIIIA-48 and -158) were commonly observed. All patients with FcγRIIIA-158F/F were always FcγRIIIA-48L/L, and patients with either FcγRIIIA-L/R or -L/H always expressed at least one valine at FcγRIIIA-158 (p≤0.001). RESULTS Major responses were higher in patients with FcγRIIIA-48L/H or -L/R (35%) versus -48L/L (22.0%) (p=NS), and among patients with FcγRIIIA-158V/V or -V/F (36%) versus -158F/F (9.0%) (p=0.03). Major responses for FcγRIIIA-48L/L patients were higher (36.8 vs. 9.0%; p=0.05) when at least one valine was present at FcγRIIIA-158, and were on par with FcγRIIIA-48L/R or -L/H patients (35.3%; p=NS) who always were FcγRIIIA-158V/V or -V/F, thereby supporting a primary role for FcγRIIIA-158 polymorphisms in predicting rituximab responses. With a median follow-up of 13 months, time to disease progression was 13 and 8 months for patients with FcγRIIIA-158V/V or V/F and -158F/F, respectively (p=NS). CONCLUSIONS The results of these studies therefore support a predictive role for FcγRIIIA-158 polymorphisms and major responses to rituximab inWM. No significant financial relationships to disclose.