Bortezomib for the treatment of non-Hodgkin’s lymphoma

Prithviraj BoseVirginia Commonwealth University, Massey Cancer Center, Richmond, VA, USA;Virginia Commonwealth University, Department of Internal Medicine, Richmond, VA, USA

Michael S BataloVirginia Commonwealth University, Department of Internal Medicine, Richmond, VA, USA

Beata HolkovaVirginia Commonwealth University, Massey Cancer Center, Richmond, VA, USA;Virginia Commonwealth University, Department of Internal Medicine, Richmond, VA, USA

Steven GrantVirginia Commonwealth University, Massey Cancer Center, Richmond, VA, USA;Virginia Commonwealth University, Department of Internal Medicine, Richmond, VA, USA;Virginia Commonwealth University, Department of Microbiology and Immunology, Richmond, VA, USA;Virginia Commonwealth University, Department of Biochemistry and Molecular Biology, Richmond, VA, USA;Virginia Commonwealth University, Department of Human and Molecular Genetics, Richmond, VA, USA;Virginia Commonwealth University, Institute for Molecular Medicine, 401 College Street, P.O. Box 980035, Richmond, VA 23298, USA+1 804 828 5211; [email protected]

, MD

Abstract

Introduction: Bortezomib, the first proteasome inhibitor (PI) to be evaluated in humans, is approved in the USA and Europe for the treatment of patients with multiple myeloma, and in the USA for patients with relapsed mantle cell lymphoma (MCL).

Areas covered: This review examines the role of bortezomib in the therapy of non-Hodgkin’s lymphoma (NHL). Bortezomib may be particularly effective against the NF-κB-dependent activated B-cell subtype of diffuse large B-cell lymphoma. The combination of bortezomib with rituximab and dexamethasone represents a standard approach for the treatment of Waldenström’s macroglobulinemia, and that with bendamustine and rituximab has demonstrated excellent efficacy in follicular lymphoma. Combinations with other novel agents, such as inhibitors of cyclin-dependent kinases or histone deacetylases, also hold substantial promise in NHL. Unmet needs in NHL, competitor compounds, chemistry, pharmacokinetics, pharmacodynamics and safety and tolerability of bortezomib are also discussed.

Expert opinion: The success of bortezomib in MCL has validated the proteasome as a therapeutic target in NHL. Rational combinations, for example, with Bruton’s tyrosine kinase inhibitors or BH3-mimetics, may hold the key to optimizing the therapeutic potential of PIs in NHL. Future trials are likely to involve newer agents with improved pharmacodynamic (e.g., carfilzomib, marizomib) or pharmacokinetic (e.g., ixazomib, oprozomib) properties.

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Bortezomib for the treatment of non-Hodgkin’s lymphoma

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Bortezomib for the treatment of non-Hodgkin’s lymphoma

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