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Abstract NHL is a heterogeneous group of lymphoproliferative disorders originating in B-lymphocytes, T-lymphocytes or NK lymphocytes. In the United States, B-cell lymphomas represent 80-85% of the cases. NHL accounted for 4% of new cancer cases and 3% of cancer deaths, making it the seventh leading cause of new cancer cases among men and women.. The treatment of NHL in the last two decades have heralded an era of increasing exploration of therapies derived from improved biologic understanding of tumors and tumor-host interactions. The focus of drug discovery has moved from identifying classical cytotoxic agents to molecules that target specific pathways involved in signal transduction, apoptosis, and differentiation. These efforts have been greatly aided by insights into the structure of proteins and the ability to design specific inhibitors using small molecules or monoclonal antibodies. These novel agents can be broadly categorized into two groups: The first is by immunotherapy which includes novel MAb and IMiDs. The other group of drugs target small molecules that may play an important role in tumorigenesis. There are an unprecedented number of ongoing clinical trials in NHL evaluating various novel targeted therapies, several of which show early evidence of efficacy. However, it is still unclear how to optimally incorporate many of these agents into treatment algorithms for NHL. The principal challenge facing investigators and clinicians, given the heterogeneity of the disease, will be the development of rational combinations that are most effective with limited toxicity, and individualizing treatment algorithms based on the biology of specific NHL. |