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Bortezomib in Relapsed and Relapsed/Refractory Multiple Myeloma

  • Jatin J. Shah
  • Robert Z. Orlowski
Chapter
Part of the Milestones in Drug Therapy book series (MDT)

Abstract

Proteasome inhibition was validated as a rational therapeutic approach when bortezomib (VELCADE®), the first-in-class proteasome inhibitor, was approved by the Food and Drug Administration in 2003. This initial approval, which was for multiple myeloma patients who had received at least two prior therapies, and whose disease had demonstrated progression on the last of these, also made bortezomib the first new agent to be available for myeloma in over a decade. Since that time, further studies of bortezomib both alone, and as part of rationally designed, molecularly based combination regimens, have shown the versatility of this agent, and made it a universally accepted standard of care. Importantly, this use of bortezomib has been associated with ever increasing overall response rates and response qualities, and, most importantly, long-term outcome measures, including overall survival. These findings have rightfully entrenched bortezomib as one of the most important parts of our chemotherapeutic armamentarium against multiple myeloma. In this chapter, we will review the role of bortezomib as a single-agent, and in combination with other chemotherapeutics, to combat myeloma in the relapsed and relapsed/refractory settings. Also, emerging data about retreatment with bortezomib will be presented to provide insights into the possible role of this agent in the modern era, in which patients may have already been previously treated as part of induction therapy with bortezomib. Finally, approaches that show promise to overcome primary or secondary resistance to bortezomib will be examined, to determine if this agent may be of benefit in a number of myeloma settings in each individual patient.

Keywords

Overall Survival Multiple Myeloma Overall Response Rate Aggresome Formation Refractory Myeloma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

J.J.S. would like to acknowledge support from the National Cancer Institute (P01 CA124787). R.Z.O., a Leukemia & Lymphoma Society Scholar in Clinical Research, and would also like to acknowledge support from the National Cancer Institute (R01 CA102278 and P01 CA124787).

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© Springer Basel AG 2011

Authors and Affiliations

  1. 1.Department of Lymphoma & Myeloma, Division of Cancer MedicineThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  2. 2.Department of Experimental Therapeutics, Division of Cancer MedicineThe University of Texas M. D. Anderson Cancer CenterHoustonUSA

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