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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Despite significant therapeutic advances in the treatment of patients with aggressive type of non-Hodgkin lymphoma (NHL), up to 40% of patients relapse following standard-of-care chemo-immunotherapy (CIT). Management of relapsed and/or refractory (R/R) DLBCL and other types of aggressive NHL is challenging as no standard of care treatment has been defined in this setting. The overall survival (OS) in refractory disease is rather poor with treatment response and duration often decreasing with each subsequent relapse. Such patients are often referred to a clinical trial program with the hope to improve outcomes with new drugs. Thus, treatment failures are by default the highest priority for the clinical trial investigation. Fortunately, recent decades heralded the development of a spectrum of novel therapeutic modalities for R/R NHL directed against a variety of targets including 1) cell surface (eg, monoclonal antibodies), 2) intracellular pathways (eg, Bruton’s tyrosine kinase [BTK], phosphoinositide 3-kinase [PI3K], spleen tyrosine kinase [SYK] and B-cell lymphoma/leukemia 2 [Bcl-2], 3) microenvironment (lenalidomide, PD-1 pathway). In parallel, therapeutic options favoring a specific subtype of DLBCL based on the cell of origin (COO), germinal center B-cell (GCB) vs. activated B-cell (ABC)as identified by gene expression profiling (GEP) platforms, are emerging to facilitate patient selection and optimize responses. Natalie Galanina1 and Rouslan Kotchetkov2* 2016-04-07T21:41:23+05:30 2016-04-07T21:41:24+05:30 2016-04-07T21:41:24+05:30 4 Adobe InDesign CS6 (Windows) uuid:9a235adf-f64d-49ea-a293-2aefaae07b72 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.id:DC3D2642DBFCE5119ADBC8BC59F48943 proof:pdf converted from application/x-indesign to application/pdf Adobe InDesign CS6 (Windows) / 2016-04-07T21:41:23+05:30 xmp.iid:DB3D2642DBFCE5119ADBC8BC59F48943 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 default Rouslan Kotchetkov, MD, PhD, Simcoe Muskoka Regional CancerProgram, Barrie, ON, Canada, E-mail: KotchetkovR@rvh.on.ca Citation: Kotchetkov R, Galanina N (2016) TheChanging Landscape of Relapsed/Refractory Non-Hodgkin Lymphoma. 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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Despite significant therapeutic advances in the treatment of patients with aggressive type of non-Hodgkin lymphoma (NHL), up to 40% of patients relapse following standard-of-care chemo-immunotherapy (CIT). Management of relapsed and/or refractory (R/R) DLBCL and other types of aggressive NHL is challenging as no standard of care treatment has been defined in this setting. The overall survival (OS) in refractory disease is rather poor with treatment response and duration often decreasing with each subsequent relapse. Such patients are often referred to a clinical trial program with the hope to improve outcomes with new drugs. Thus, treatment failures are by default the highest priority for the clinical trial investigation. Fortunately, recent decades heralded the development of a spectrum of novel therapeutic modalities for R/R NHL directed against a variety of targets including 1) cell surface (eg, monoclonal antibodies), 2) intracellular pathways (eg, Bruton’s tyrosine kinase [BTK], phosphoinositide 3-kinase [PI3K], spleen tyrosine kinase [SYK] and B-cell lymphoma/leukemia 2 [Bcl-2], 3) microenvironment (lenalidomide, PD-1 pathway). In parallel, therapeutic options favoring a specific subtype of DLBCL based on the cell of origin (COO), germinal center B-cell (GCB) vs. activated B-cell (ABC)as identified by gene expression profiling (GEP) platforms, are emerging to facilitate patient selection and optimize responses. Natalie Galanina1 and Rouslan Kotchetkov2* 2016-04-07T21:41:23+05:30 2016-04-07T21:41:27+05:30 2016-04-07T21:41:27+05:30 4 Adobe InDesign CS6 (Windows) uuid:7873fb6c-cff6-487a-b789-31b650916d52 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.id:DC3D2642DBFCE5119ADBC8BC59F48943 proof:pdf converted from application/x-indesign to application/pdf Adobe InDesign CS6 (Windows) / 2016-04-07T21:41:23+05:30 xmp.iid:DB3D2642DBFCE5119ADBC8BC59F48943 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 xmp.did:FE00469DB0C7E411AEB789ACBE3823B3 default Rouslan Kotchetkov, MD, PhD, Simcoe Muskoka Regional CancerProgram, Barrie, ON, Canada, E-mail: KotchetkovR@rvh.on.ca Citation: Kotchetkov R, Galanina N (2016) TheChanging Landscape of Relapsed/Refractory Non-Hodgkin Lymphoma. 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