Bortezomib in the front-line treatment of multiple myeloma

Abstract

Front-line therapy for multiple myeloma is rapidly evolving with the development of new, highly active regimens based on novel agents such as bortezomib. Bortezomib-based regimens are demonstrating substantial efficacy both as induction prior to stem cell transplantation and as treatment for patients ineligible for transplant, offering rapid and durable responses with consistently high rates of complete response, a surrogate end point for improved overall survival. Combinations of bortezomib plus established and novel agents, such as melphalan–prednisone, dexamethasone, doxorubicin, thalidomide–dexamethasone and, most recently, lenalidomide–dexamethasone, are proving superior to or more promising than previous standards of care. Importantly, these regimens are demonstrating enhanced activity across the front-line population, including patients with renal impairment, high-risk cytogenetics and advanced bone disease. Impressive Phase 3 results with bortezomib–melphalan–prednisone, bortezomib–dexamethasone and bortezomib–thalidomide–dexamethasone should facilitate the establishment of these highly effective regimens as key therapies for newly diagnosed myeloma.

Keywords::

• 26S proteasome
• bortezomib
• combination therapy
• front line
• induction therapy
• multiple myeloma
• proteasome inhibitor
• stem cell transplantation

Acknowledgements

The authors gratefully acknowledge Steve Hill and Jane Saunders for editorial assistance in drafting this manuscript, and Caitlin Conant for administrative assistance.

Financial & competing interests disclosure

Kenneth C Anderson and Constantine Mitsiades have received consultant honoraria from Millennium Pharmaceuticals. Constantine Mitsiades has received consultant honoraria from Pharmion. Kenneth C Anderson, Paul G Richardson, Robert Schlossman, Nikhil Munshi and Irene Ghobrial are members of the speakers’ bureau for Millennium Pharmaceuticals. Paul G Richardson, Robert Schlossman, Nikhil Munshi and Irene Ghobrial are members of the speakers’ bureau for Celgene. Paul G Richardson is a member of the speakers’ bureau for Johnson & Johnson. Irene Ghobrial and Kenneth C Anderson have received research funding from Millennium Pharmaceuticals. Irene Ghobrial has received research funding from Keryx Pharmaceuticals. Paul G Richardson has participated in advisory boards for Millennium Pharmaceuticals and Celgene.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No paid writing assistance was provided for the production of this manuscript.