학술논문
Polymorphisms in FcγRIIIA (CD16) Receptor Expression Are Associated With Clinical Response to Rituximab in Waldenströmʼs Macroglobulinemia
Document Type
Academic Journal
Author
Source
Journal of Clinical Oncology. Jan 20, 2005 23(3):474-481
Subject
Language
English
ISSN
0732-183X
Abstract
PURPOSE: Rituximab is an important therapeutic for Waldenströmʼs macroglobulinemia (WM). Polymorphisms in FcγRIIIA (CD16) receptor expression modulate human immunoglobulin G1 binding and antibody-dependent cell-mediated cytotoxicity, and may therefore influence responses to rituximab. PATIENTS AND METHODS: Sequence analysis of the entire coding region of FcγRIIIA was undertaken in 58 patients with WM whose outcomes after rituximab were known. RESULTS: Variations in five codons of FcγRIIIA were identified. Two were commonly observed (FcγRIIIA-48 and FcγRIIIA-158) and predicted for amino acid polymorphisms at FcγRIIIA-48: leucine/leucine (L/L), leucine/arginine (L/R), and leucine/histidine (L/H). Polymorphisms at FcγRIIIA-158 were phenylalanine/phenylalanine (F/F), phenylalanine/valine (F/V), and valine/valine (V/V). A clear linkage between these polymorphisms was detected and 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 ≤ .001). The response trend was higher for patients with FcγRIIIA-48L/H (38.5%) versus -48L/R (25.0%) and LL (22.0%), and was significantly higher for patients with FcγRIIIA-158V/V (40.0%) and -V/F (35%) versus -158F/F (9.0%; P = .030). Responses for patients with FcγRIIIA-48L/L were higher when at least one valine was present at FcγRIIIA-158 (P = .057), thereby supporting a primary role for FcγRIIIA-158 polymorphisms in predicting rituximab responses. With a median follow-up of 13 months, no significant differences in the median time to progression and progression-free survival were observed when patients were grouped according to their FcγRIIIA-48 and -158 polymorphisms. CONCLUSION: The results of these studies therefore support a predictive role for FcγRIIIA-158 polymorphisms and responses to rituximab in WM.