Lijuan Deng

FCGR3A 158V/F Polymorphism and Response to Frontline R-CHOP Therapy in Diffuse Large B-Cell Lymphoma

The influence of Fc gamma receptor IIIA (FCGR3A) 158V/F polymorphisms on the response to rituximab (R) plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone; R-CHOP) therapy in diffuse large B-cell lymphoma (DLBCL) is uncertain. Thus, a retrospective study and a meta-analysis were performed to examine the possible correlation between FCGR3A 158V/F polymorphism and the response rate of R-CHOP regimen in patients with newly diagnosed DLBCL. The genotypes of FCGR3A 158V/F in 164 newly diagnosed DLBCL patients treated with R-CHOP were determined in this retrospective study. Additionally, a meta-analysis of current and previously published studies was conducted. Overall response rate (complete and partial response, ORR) and complete response rate (CR) were evaluated. The results of our retrospective study showed lack of correlation between FCGR3A 158V/F polymorphism and ORR (p=0.78) or CR (p=0.76) with R-CHOP therapy. A meta-analysis of 731 cases also showed lack of significant association of ORR and CR in all genetic models with FCGR3A 158V/F polymorphism. In survival analysis, the homozygous F genotype correlated with a shorter progression-free survival than that of non-F/F genotype (p=0.05), this was significant for the non-GC subset of DLBCL (p=0.04), but no association was found between overall survival and FCGR3A 158V/F polymorphism. Further analysis with nonsuperiority test (p<0.0001) suggested that FCGR3A 158V/F polymorphism was not associated with better ORR or CR in newly diagnosed DLBCL patient treated with R-CHOP. No clear relationship was found between FCGR3A 158V/F polymorphism and response to frontline R-CHOP therapy in patients with DLBCL.

Safety and efficacy of bevacizumab combined with R-CHOP regimen in seven Chinese patients with untreated diffuse large B-cell lymphoma.

BackgroundRituximab plus CHOP (R-CHOP) significantly improved the outcome of diffuse large B cell lymphoma (DLBCL), a common sub-type of non-Hodgkin lymphoma. But 40% – 50% of DLBCL patients cannot be cured by this regimen. Some clinical trials showed that bevacizumab might be useful in the treatment of DLBCL. This study evaluated the safety and efficacy of bevacizumab combined with the R-CHOP (A-R-CHOP) regimen in Chinese patients with previously untreated DLBCL.MethodsPatients with previously untreated DLBCL received A-R-CHOP regimen therapy. All patients with complete response (CR)/ unconfirmed complete response(CRu) after 8 cycles of A-R-CHOP received the bevacizumab maintenance therapy once every 3 weeks. The remained bulky disease was treated with radiotherapy.ResultsSeven Chinese patients were treated. All of them had bulky diseases. One patient had progressive disease after 4 cycles of A-R-CHOP therapy. The rest six patients completed 8 cycles of A-R-CHOP treatment. All of these six patients reached CR/CRu (5 CR, 1 CRu). Bevacizumab maintenance therapy was given to 4 CR patients. All 7 patients experienced Grade 3/4 hematologic adverse events; additionally, one had Grade 3 gastrointestinal toxicity and one had Grade 1 epistaxis. During bevacizumab maintenance therapy, one patient had Grade 1 gingival bleeding, another experienced Grade 1 proteinuria and then Grade 3 congestive heart failure 4 months after completion of maintenance therapy. At the end of July 2013, the patient who had progressive disease after 4 cycles of A-R-CHOP died of progressive disease, the other six remained CR response.ConclusionsThe A-R-CHOP regimen is effective for untreated DLBCL, but may cause bevacizumab-specific toxicities, which should be monitored.

CD3+/CD8+ T-cell density and tumoral PD-L1 predict survival irrespective of rituximab treatment in Chinese diffuse large B-cell lymphoma patients

To investigate the prognostic value of tumor-infiltrating T-cell density and programmed cell death ligand-1 (PD-L1) expression in diffuse large B cell lymphoma (DLBCL). One-hundred-twenty-five Chinese DLBCL patients were enrolled in our study and provided samples; 76 of all cases were treated with rituximab (R). Tumor tissues were immunostained and analyzed for CD3+ and CD8+ tumor-infiltrating T-cell density, tumoral PD-L1, and microenvironmental PD-L1 (mPD-L1). The density of CD3 was rated as high in 33.6% cases, while 64.0% of DLBCLs were classified as high CD8 density. Of all cases, 16.8% were PD-L1+. Of the remaining PD-L1–DLBCLs, 29.8% positively expressed mPD-L1. Both CD3 high density and CD8 high density were associated with mPD-L1 positivity (P = 0.001 and P = 0.0001). In multivariate analysis, independently, high CD3 density predicted better OS (P = 0.023), while CD8 high density and PD-L1 positivity were both associated with prolonged PFS (P = 0.013 and P = 0.036, respectively). Even in the subgroup treated with R, univariate analyses indicated that high CD3 density and PD-L1 positivity were associated with better OS (P = 0.041) and PFS (P = 0.033), respectively. The infiltrating densities of CD3+ T-cells, CD8+ T-cells, and PD-L1 expression are predictive of survival in DLBCLs, irrespective of R usage.

A PHASE I STUDY OF CHIMERIC ANTIGEN RECEPTORMODIFIED T CELLS DIRECTED AGAINST CD19 IN PATIENTS WITH RELAPSED OR REFRACTORYCD19(+) B CELL LYMPHOMAS: INTERIM ANALYSIS

271 A PHASE I STUDY OF CHIMERIC ANTIGEN RECEPTORMODIFIED T CELLS DIRECTED AGAINST CD19 IN PATIENTS WITH RELAPSED OR REFRACTORYCD19(+) B CELL LYMPHOMAS: INTERIM ANALYSIS Z. Ying* | X. Xiang | Y. Song | N. Ding | Y. Lin | W. Zheng | X. Wang | N. Lin | M. Tu | Y. Xie | C. Zhang | W. Liu | L. Deng | Y. Liu | Y. Yue | X. Yu | H. Liu | P. Duan | F. Chen | X. Wu | X.F. Huang | L. Jones | X. Kang | S. Chen | J. Zhu Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China; Department of medicine, Marino Biotechnology Co., Ltd., Beijing, China; Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, USA

TP53 Arg72 as a favorable prognostic factor for Chinese diffuse large B-cell lymphoma patients treated with CHOP

BackgroundTP53 Arg72Pro (SNP rs1042522) is associated with risk of non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of NHL. However, the relationship between this SNP and prognosis of DLBCL in Asians is unknown.MethodsGenotyping of TP53 Arg72Pro was done in 425 Chinese DLBCL patients. Two hundred and eighty-nine patients were treated with R-CHOP, and 136 patients received CHOP or CHOP-like as frontline regimen. Three hundred and ninety-six patients were assessable for the efficacy.ResultsPatients with Arg/Arg and Arg/Pro at codon 72 of TP53 had a higher complete response rate (61% vs. 44%, P = 0.007) than those with Pro/Pro. In the subgroup treated with CHOP or CHOP-like therapy, patients with Arg/Arg and Arg/Pro showed a higher 5-year overall survival (OS) rate than those with Pro/Pro (68.8% vs. 23.2%, P = 0.001). Multivariate Cox regression analysis revealed TP53 Arg72 as a favorable prognostic factor in this group. However, the combination of rituximab with CHOP significantly increased the 5-year OS rate of patients with Pro/Pro to 63%.ConclusionThis study revealed TP53 Arg72 as a favorable prognostic factor for Chinese DLBCL patients treated with CHOP or CHOP-like as frontline therapy.