Contributions
Abstract: PB2032
Type: Publication Only
Background
The effectiveness of targeted therapy of non-Hodgkin's malignant lymphomas with monoclonal antibody (MCA) rituximab has been showed in many randomized clinical trials. Nevertheless, a number of patients have resistance to this class of drugs, which may be associated with the inherent characteristics of the receptor of immune cells. Therefore, it seems relevant to study the genetic polymorphism of Fcɣ-receptors, whose carriage affects this mechanism of action of MCA as an antibody-dependent cellular cytotoxicity.
Aims
To study the impact of Fcɣ receptor SNP (FcɣIIIRa) on the results of rituximab therapy in patients with B-cell non-Hodgkin's malignant lymphomas (NHL).
Methods
191 patients from the City Hematology Center of Novosibirsk with a diagnosis of B-cell NHL were examined. Aggressive lymphomas were verified in 118 patients (61.8%), indolent lymphomas were diagnosed in 73 patients (38.2%). All patients received from 6 to 12 courses of polychemotherapy comprising rituximab. Genotyping of Fcɣ receptor SNP was performed using Taq-man PCR. The significance of the differences was assessed using the χ2 criterion, the differences at p <0.05 were considered statistically significant.
Results
The distribution of the genotypes of the FcIIIRa gene in the aggressive lymphoma group was as follows: 53 patients (45%) have the wild T/T genotype, 57 persons (48.3%) have the T/G genotype, 8 (6.7%) patients have rare G/G genotype. In this group of NHL a complete or partial response to therapy was achieved in 78.6% of patients, relapse or progression of the disease was observed in 21.4% of the patients. During the statistical analysis the effect of this polymorphic locus on the results of therapy with aggressive lymphomas was not detected. In the group with indolent NHL 25 (35.6%) patients have the wild T/T genotype, 34 (46.6%) persons have the T/G genotype, 13 (17,8%) patients have the rare G/G genotype. In this group of NHL complete or partial response to therapy was achieved in 76.7% of patients, relapse or progression of the disease was noted in 23.3% of patients. It was revealed that the "rare" genotype FcγRIIIa was statistically significantly associated with an unfavorable outcome of the disease (p<0.05) in patients with indolent variants of NHL. The literature data on the effect of the FcγRIIIa polymorphic locus on the therapy effectiveness of indolent lymphomas are inconsistent, which may be due to genetic heterogeneity of populations and require a meta-analysis in which the results of this study may be included.
Conclusion
The correlation between the "rare" genotype of the FcɣIIIRa polymorphic loci and the treatment failure in the group of patients with indolent lymphomas is shown, which allows considering this SNP as a potential marker of effeciency of treatment with rituximab.
Session topic: 20. Indolent Non-Hodgkin lymphoma – Clinical
Keyword(s): FcGRIIIa polymorphism, Non-Hodgkin's lymphoma, Rituximab
Abstract: PB2032
Type: Publication Only
Background
The effectiveness of targeted therapy of non-Hodgkin's malignant lymphomas with monoclonal antibody (MCA) rituximab has been showed in many randomized clinical trials. Nevertheless, a number of patients have resistance to this class of drugs, which may be associated with the inherent characteristics of the receptor of immune cells. Therefore, it seems relevant to study the genetic polymorphism of Fcɣ-receptors, whose carriage affects this mechanism of action of MCA as an antibody-dependent cellular cytotoxicity.
Aims
To study the impact of Fcɣ receptor SNP (FcɣIIIRa) on the results of rituximab therapy in patients with B-cell non-Hodgkin's malignant lymphomas (NHL).
Methods
191 patients from the City Hematology Center of Novosibirsk with a diagnosis of B-cell NHL were examined. Aggressive lymphomas were verified in 118 patients (61.8%), indolent lymphomas were diagnosed in 73 patients (38.2%). All patients received from 6 to 12 courses of polychemotherapy comprising rituximab. Genotyping of Fcɣ receptor SNP was performed using Taq-man PCR. The significance of the differences was assessed using the χ2 criterion, the differences at p <0.05 were considered statistically significant.
Results
The distribution of the genotypes of the FcIIIRa gene in the aggressive lymphoma group was as follows: 53 patients (45%) have the wild T/T genotype, 57 persons (48.3%) have the T/G genotype, 8 (6.7%) patients have rare G/G genotype. In this group of NHL a complete or partial response to therapy was achieved in 78.6% of patients, relapse or progression of the disease was observed in 21.4% of the patients. During the statistical analysis the effect of this polymorphic locus on the results of therapy with aggressive lymphomas was not detected. In the group with indolent NHL 25 (35.6%) patients have the wild T/T genotype, 34 (46.6%) persons have the T/G genotype, 13 (17,8%) patients have the rare G/G genotype. In this group of NHL complete or partial response to therapy was achieved in 76.7% of patients, relapse or progression of the disease was noted in 23.3% of patients. It was revealed that the "rare" genotype FcγRIIIa was statistically significantly associated with an unfavorable outcome of the disease (p<0.05) in patients with indolent variants of NHL. The literature data on the effect of the FcγRIIIa polymorphic locus on the therapy effectiveness of indolent lymphomas are inconsistent, which may be due to genetic heterogeneity of populations and require a meta-analysis in which the results of this study may be included.
Conclusion
The correlation between the "rare" genotype of the FcɣIIIRa polymorphic loci and the treatment failure in the group of patients with indolent lymphomas is shown, which allows considering this SNP as a potential marker of effeciency of treatment with rituximab.
Session topic: 20. Indolent Non-Hodgkin lymphoma – Clinical
Keyword(s): FcGRIIIa polymorphism, Non-Hodgkin's lymphoma, Rituximab