Bortezomib: A Proteasome Inhibitor with An Evolving Role in Select Subtypes of B-Cell Non-Hodgkin’s Lymphoma

Bortezomib is a novel proteasome inhibitor initially approved for use in multiple myeloma and currently under continued investigation as a treatment for numerous subtypes of non-Hodgkin's lymphoma. One postulated mechanism of action in non-Hodgkin's lymphoma is the ability of bortezomib to ameliorate molecular dysregulation in NF-κB activation and regain cell cycle control. Results of clinical trials have varied widely based on lymphoma subtype. While response to bortezomib has been dismal in chronic lymphocytic leukemia and small lymphocytic lymphoma, reasonable responses have been attained in mantle cell lymphoma leading to its US FDA approval as a second-line agent for the treatment of mantle cell lymphoma in 2006. Bortezomib in combination with R-CHOP has also been suggested to improve response in certain molecular subgroups of diffuse large B-cell lymphoma. The role of bortezomib in follicular and marginal zone lymphomas remains less clear.