Project description:Peripheral blood was collected into PAXgene tubes from 7 patients with follicular lymphoma, in a phase 2 clinical trial of lenalidomide plus rituximab as initial therapy for advanced-stage indolent non-Hodgkin's lymphoma. Blood was collected at baseline and on Day 15 of the second 28-day cycle, for determination of the gene expression profile after globin mRNA reduction.
Project description:Peripheral blood was collected into PAXgene tubes from 7 patients with follicular lymphoma, in a phase 2 clinical trial of lenalidomide plus rituximab as initial therapy for advanced-stage indolent non-Hodgkin's lymphoma. Blood was collected at baseline and on Day 15 of the second 28-day cycle, for determination of the gene expression profile after globin mRNA reduction. The effect of treatment on gene expression profiles was largely based on the paired t test, using the Significance Analysis of Microarrays method.
Project description:This SuperSeries is composed of the following subset Series: GSE3646: Follicular lymphoma and normal lymphoid tissue comparisons GSE3647: Follicular lymphoma lymph node Abstract: Analysis of the patterns of gene expression in follicular lymphomas from 24 patients suggested that two groups of tumors might be distinguished. All patients, whose biopsies were obtained before any treatment, were treated with rituximab, a monoclonal antibody directed against the B cell antigen, CD20. Gene expression patterns in the tumors that subsequently failed to respond to rituximab appeared more similar to those of normal lymphoid tissues than to gene expression patterns of tumors from rituximab responders. These findings suggest the possibility that the response of follicular lymphoma to rituximab treatment may be predicted from the gene expression pattern of tumors. Refer to individual Series
Project description:Endogenous or iatrogenic antitumor immune responses can improve the course of follicular lymphoma (FL), but may be diminished by immunoregulatory mechanisms in the tumor microenvironment. These may include effects of programmed death (PD)-1, a coinhibitory receptor that impairs T-cell function and is highly expressed on intratumoral T cells. In a Phase II trial, we tested the efficacy of pidilizumab, a humanized anti-PD-1 monoclonal antibody, with rituximab in patients with rituximab-sensitive FL relapsed after 1-4 prior therapies. Pidilizumab was administered at 3 mg/kg every 4 weeks for 4 infusions, plus 8 optional infusions every 4 weeks for patients with stable disease or better. Starting 2 weeks after the first infusion of pidilizumab, rituximab was given at 375 mg/m2 weekly for 4 weeks. Peripheral blood and tumor biopsies were studied to assess immunological effects of pidilizumab. The combination was well-tolerated, with no grade 3/4 toxicities. Overall (66%) and complete (52%) response rates in 29 evaluable patients were high, with tumor regression in 86% of patients. Median progression-free survival was 18.8 months, and was not reached for the 19 responders. Peripheral blood immunophenotyping showed increased memory CD4+ T cells and activation of NK cells after pidilizumab therapy. Tumor response and progression-free survival were associated with T-cell activation gene signatures in tumor gene expression profiling data, both at baseline and in changes induced by pidilizumab. The efficacy of pidilizumab with rituximab compared favorably to historical retreatment with rituximab monotherapy in patients with relapsed FL. Pidilizumab may benefit patients with pre-existing endogenous antitumor immune responses. This set contains 26 samples in total. 8 pairs of pre- and post-treatment samples, and 10 additional pre-treatment samples.
Project description:Endogenous or iatrogenic antitumor immune responses can improve the course of follicular lymphoma (FL), but may be diminished by immunoregulatory mechanisms in the tumor microenvironment. These may include effects of programmed death (PD)-1, a coinhibitory receptor that impairs T-cell function and is highly expressed on intratumoral T cells. In a Phase II trial, we tested the efficacy of pidilizumab, a humanized anti-PD-1 monoclonal antibody, with rituximab in patients with rituximab-sensitive FL relapsed after 1-4 prior therapies. Pidilizumab was administered at 3 mg/kg every 4 weeks for 4 infusions, plus 8 optional infusions every 4 weeks for patients with stable disease or better. Starting 2 weeks after the first infusion of pidilizumab, rituximab was given at 375 mg/m2 weekly for 4 weeks. Peripheral blood and tumor biopsies were studied to assess immunological effects of pidilizumab. The combination was well-tolerated, with no grade 3/4 toxicities. Overall (66%) and complete (52%) response rates in 29 evaluable patients were high, with tumor regression in 86% of patients. Median progression-free survival was 18.8 months, and was not reached for the 19 responders. Peripheral blood immunophenotyping showed increased memory CD4+ T cells and activation of NK cells after pidilizumab therapy. Tumor response and progression-free survival were associated with T-cell activation gene signatures in tumor gene expression profiling data, both at baseline and in changes induced by pidilizumab. The efficacy of pidilizumab with rituximab compared favorably to historical retreatment with rituximab monotherapy in patients with relapsed FL. Pidilizumab may benefit patients with pre-existing endogenous antitumor immune responses.
Project description:Abstract: Analysis of the patterns of gene expression in follicular lymphomas from 24 patients suggested that two groups of tumors might be distinguished. All patients, whose biopsies were obtained before any treatment, were treated with rituximab, a monoclonal antibody directed against the B cell antigen, CD20. Gene expression patterns in the tumors that subsequently failed to respond to rituximab appeared more similar to those of normal lymphoid tissues than to gene expression patterns of tumors from rituximab responders. These findings suggest the possibility that the response of follicular lymphoma to rituximab treatment may be predicted from the gene expression pattern of tumors. This SuperSeries is composed of the SubSeries listed below.
Project description:Purpose: the goal of this study is to analyze the effect of lenalidomide on CD4pos PD-1pos, CD4pos PD-1neg, CD8pos PD-1neg and CD8pos PD-1pos subsets Methods: genome-wide mRNA profiles of 6 first-line follicular lymphoma patients (GALEN protocol) were generated using deep sequencing before and after one-week lenalidomide, using Illumina HiSEq4000. All paired-end sequence reads passed quality filters.and were analyzed at the gene level with STAR followed by Featurecount. Results: Important differences in functional biological pathways related to proliferation, immune system, metabolism and immune synapse in PD-1pos T-cells triggered by lenalidomide were highlighted by the experiment.
Project description:We used gene expression profiling and pathway impact analyses to search signaling pathways, which mediate crosstalk between lymphoma cells and tumor-infiltrating inflammatory cells and contribute to the outcome of follicular lymphoma (FL) patients. 24 FL patients treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy were classified into groups of favorable or adverse outcomes, and the transcripts differentially expressed in the pretreatment FL tissues between the groups were analyzed.
Project description:This phase I/II trial studies the side effects and best dose of romidepsin and lenalidomide when combined with rituximab and to see how well this combination works in treating patients with B-cell non-Hodgkin lymphoma that has returned (recurrent) or did not respond to treatment (refractory). Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Romidepsin and lenalidomide may stop the growth of cancer cells by blocking enzymes needed for cell growth. Giving rituximab together with romidepsin and lenalidomide may be a better treatment for B-cell non-Hodgkin lymphoma.
Project description:This phase II trial studies how well giving lenalidomide with or without rituximab works in treating patients with progressive or relapsed chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), prolymphocytic leukemia (PLL), or non-Hodgkin lymphoma (NHL). Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving lenalidomide together with or without rituximab may kill more cancer cells.