Exploratory Study on the Relationship Between FcγRIIIa Gene Polymorphisms and the Efficacy and Toxicity of Rituximab in the Treatment of Stage I/II Diffuse Large B-Cell Lymphoma

Abstract

Rituximab is an IgG1 monoclonal antibody approved for the treatment of diffuse large B-cell lymphoma (DLBCL); however, its efficacy is poor in some patients. Previous studies indicate that the difference in efficacy may be due to antibody-dependent cell-mediated cytotoxicity (ADCC). The effect of ADCC is closely related to Fcγ receptor IIIA (FcγRIIIa) receptor gene polymorphisms, but no study has investigated this gene in patients with DLBCL in China. In this study, we explored FcγRIIIa gene polymorphisms in patients with DLBCL in China and the ethnic differences in the FcγRIIIa gene. Moreover, we determined the relationship between FcγRIIIa gene polymorphisms and the effect and toxicity of rituximab treatment. Peripheral blood samples of 60 patients with newly diagnosed stage I/II DLBCL who received standard treatment with rituximab were collected, and DNA samples were extracted and normalized. Among the FcγRIIIa gene polymorphisms, there was a homozygous mutation, a heterozygous mutation, and a wild-type genotype at the site of 161514542 (rs396991). The proportion of these genotypes was significantly different from those found in previous studies for European and American populations and healthy Chinese populations. Moreover, we found that individuals with the homozygous (158-V/V) or heterozygous (V/F) mutation possessed better near-term effectiveness of the standard chemotherapeutic treatment, although there was no significant difference in long-term survival. However, patients with one of these genotypes usually suffer from a more severe hematological toxicity in response to the rituximab treatment. In conclusion, knowledge of a patient's FcγRIIIa gene polymorphism may be of value for the individualized treatment of DLBCL, which is worthy of follow-up research.