Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression profiling of tumor biopsies before and after pidilizumab therapy in patients with relapsed follicular lymphoma grade 1 or grade 2.

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Min Zhang

PROVIDER: E-GEOD-52562 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Gene expression profiling of tumor biopsies before and after pidilizumab therapy in patients with relapsed follicular lymphoma grade 1 or grade 2.

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